Plasma corticosterone 1 hr post 4/g/kg EtOH [µg/dl]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD. 	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci 	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	01	65-115 days	65	115	Male	5-15	µg/dl	16.21	1.63	20.29	3.02	17.42	1.67	16.89	2.14	22.63	3.22	12.53	2.86	13.97	1.86	28.12	2.81			24.68	2.55	17.17	1.91	23.09	1.42	16.11	2.53	27.64	2.69	20.39	4.06					16.41	2.49	20.13	1.91			22.82	3.16	15.07	4.75	24.24	3.18	24.03	2.00	16.34	2.04																													12/26/2002			ETCORT4(1H)		ETCORT1	EtOH	4g/kg		JKB/AR	p. 1202, Fig 1	MRG 020402 with JKB by publication	8748968.01
Plasma corticosterone 1 hr post saline [µg/dl]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci 	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	03	65-115 days	65	115	Male	3-9	µg/dl	4.36	0.64	4.07	1.71	4.35	2.00	8.28	3.78	3.99	1.03	8.59	4.62	15.19	5.56	5.07	0.89			5.64	1.90	2.47	0.64	6.14	1.14	6.04	2.67	7.54	3.74	1.09	0.37					5.66	2.71	4.22	0.69			6.95	1.58	11.34	8.21	11.86	9.09	7.77	2.66	2.88	0.53																													12/26/2002			SALCORT (1H)		SALCORT1	Saline			JKB/AR	p. 1202, Fig 1	MRG 020402 with JKB by publication	8748968.03
Plasma corticosterone 6 hr post ETOH Male [µg/dl] [Plasma corticosterone 6 hours post 4/g/kg EtOH (Male), Unpublished means from same series of studies as reported in:  Roberts, Phillips, Belknap, Finn, Keith 1995, Behavioral Neurosci 109:1199-1208]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci 	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	99	65-115 days	65	115	Male		µg/dl							16.4		15.3		13.9		4.5				4.7		21.9		17.7		16.5		17.7		15.3		20						13.3		12.8		16.1		14.8		8.6		21.5		16.3		11.8		18.1		9.5		15.7																								12/27/2002			SALCORT(6H)		ETCORT6	EtOH	4g/kg		JKB/AR		MRG 020402 with JKB	8748968.99
Plasma corticosterone 6 hr post EtOH Female [µg/dl] [Plasma corticosterone 6 hours post 4/g/kg EtOH (Female)Unpublished means from same series of studies as reported in:  Roberts, Phillips, Belknap, Finn, Keith 1995, Behavioral Neurosci 109:1199-1208]		The genetic control over the corticosterone response to ethanol (EtOH) and its possible relationship to other EtOH-related traits was examined using BXD recombinant inbred (RI) strains derived from an F2 cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Quantitative trait locus (QTL) analysis of corticosterone levels 1 hr following EtOH suggested the influence of a single major gene on this trait. Two loci were predicted to account for 47% of the genetic variance in plasma corticosterone levels 6 hr following EtOH, whereas 3 loci were predicted to account for 78% of the genetic variance in corticosterone levels 7 hr following EtOH. Markers associated with corticosterone levels 7 hr following EtOH and corrected corticosterone levels 6 hr post-EtOH overlapped with ones found to influence acute and chronic EtOH withdrawal severity, suggesting some degree of common genetic determination between these traits. Overall these results indicate that gene action significantly influences stress responsiveness and suggest possible chromosomal locations of these genes.	Roberts AJ, Phillips TJ, Belknap JK, Finn DA, Keith LD.  	Genetic analysis of the corticosterone response to ethanol in BXD recombinant inbred mice	Behav Neurosci	109(6)	1199-1208	Dec	1995		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8748968&dopt=Abstract	8748968	96350725	98	65-115 days	65	115	Female		µg/dl	5		9		4		9		14		8		4		10		5		22		18		12		17		7		20		13				13		9		16		12		8		21		16		12		18		10		16																								12/27/2002			SALCORT(6HF)		ETCORT6F	EtOH	4g/kg		JKB/AR		MRG 020402 with JKB	8748968.98
Audiogenic seizure-mean severity score in response to pure tone [severity of seizure] 		The difference in susceptibility to audiogenic seizures (AGS) between C57BL/6J and DBA/2J inbred strains of mice is due to multiple genetic factors. AGS susceptibility was tested in 21-day-old mice from classical crosses, BXD recombinant inbred (RI) strains, a congenic DBA/2N.B6N-Ahb inbred strain and crosses between the BXD RI strains and DBA/2J. Analysis of these data reveals that the variation in AGS susceptibility between these two strains results from allelic differences at three or more loci. Most of the variation is due to allelic differences at two loci. The first, Asp-1 (formerly Ias), is a major gene located on chromosome 12, between Ah and D12 Nyul. The second, Asp-2 (formerly asp), is a minor gene located on chromosome 4, tightly linked to b. The negative correlation of brain stem Ca2(+)-ATPase activity and AGS susceptibility in the BXD RI strains suggests that the strain difference in Ca2(+)-ATPase activity is inherited as a polygenic trait and that Asp-1 and Asp-2 are linked to, or identical to, factors that influence Ca2(+)-ATPase activity.	Neumann PE, Seyfried TN.	Mapping of two genes that influence susceptibility to audiogenic seizures in crosses of C57BL/6J and DBA/2J mice	Behav Genet 	20(2)	307-323	Mar	1990		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2141254&dopt=Abstract	2141254		01	20-22 days	20	22	MF	10-63	Severity of seizure; 0=no response, 1=wild running, 2=clonic or tonic seizure 	0.07		1.88		0.2		1.92		1.64		0.14		0.57		1.85		1.04		0.3		0.1		0.33		1.94		0.21		0.07		0.73				1.92				1.16		1.09		0.36		1.29		1		0.09		0				1.89																								6/23/2003	MK Sullivan	MK Sullivan	AGS		AGS	 	60 sec exposure to pure tone 11KHx at 120db		JKB	p. 311, Table 1	MRG 120601 from publication	2141254.01
Morphine hypothermia DRC slope			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		01				Male			-4.58		-7.01		-7.06		-5.75		-6.33		-4.88		-7.36		-2.93				-2.02		-3.43		-3.75		-1.88		-1.31		-4.53						-2.73		-2.12		-5.29		-3.54		-6.06		-5.82		-7.5		-6.06																												-7.65		12/20/2002			MORTEMP		BDTEMP30	Morphine	Dose response across 8, 16, or 32 mg/kg i.p.		JKB	p. 319, Fig 3	MRG 011002; prior confirmation by JKB with data and publication	1632590.01
Morphine analgesia DRC slope			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		02				Male			26.8		59.7		50.1		63.4		30		30.5		62.7		27.6				33.9		25.8		31.2		25.5		36.7		39.1						15.2		10.9		44.3		59.8		35.4		46.3		34.7		24.3																												42.9		12/20/2002			MORHPL8		HOTPLATE	Morphine	Dose response across 8, 16, or 32 mg/kg i.p.		JKB	p. 319, Fig 3	MRG 011002; prior confirmation by JKB with data and publication	1632590.02
Straub tail Morphine DRC slope			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		03				Male			0.94		0.25		1.37		1.04		1.07		0.94		0.42		0.75				0.81		0.94		1.37		0.91		0.73		0.98						0.48		0.61		1.2		0.35		0.75		1.16		1.24		0.75																												0.78		12/20/2002			MORSTRAUB		STRAUB30	Morphine	Dose response across 8, 16, or 32 mg/kg i.p.		JKB	p. 319, Fig 3	MRG 011002; prior confirmation by JKB with data and publication	1632590.03
Saline body temp, degree C			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		04				Male		degrees celsius	37.5		37.7		38.1		37		37.2		38.3		37.4		37.3				38.4		37.8		37.6		36.6		37		38.4						36.8		37.3		37.5		37.5		37.9		38.5		37.8		38.8																												38.2		12/20/2002			SALTEMP		SAL_BTMP	Saline			JKB		MRG 011002; prior confirmation by JKB with data and publication	1632590.04
Saline hot plate latency, seconds			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		05				Male		seconds	20.2		21.3		22		19.5		11.8		8.8		31		18				14.1		11.6		12.8		13		11.9		20						13.8		16.1		12.2		13.5		15		15.5		22.9		9.8																												19.1		12/20/2002			SALHP8		SAL_HOTP	Saline			JKB		MRG 011002; prior confirmation by JKB with data and publication	1632590.05
Saline elevated open field activity, [Unpublished means from same series of studies as reported in:  Belknap & Crabbe, 1992 ANYAS 654:311-323]			Belknap JK, Crabbe JC.	Chromosome mapping of gene loci affecting morphine and amphetamine responses in BXD recombinant inbred mice	Ann NY Acad Sci	654	311-323	Jun 	1992 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1632590&dopt=Abstract	1632590		06				Male			15.44		6.39		9.34		12.15		9.24		15.25		8.4		8.675				14.49		6.43		11.84		7.315		10.25		12.72						7.95		8.3		5.925		6.945		8.26		8.58		5.25		12																														12/20/2002			SALACT(EOF)		SALACT	Saline			JKB		MRG 020402 with JKB	1632590.06
Baseline handling induced convulsions (HIC) 		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet 	23(2)	213-222	Mar	1993		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		01	100 days			Male			0.6995		0.3415		1.6835		2.0565		1.17045		0.3985		1.146		1.8895				0.6495		1.581		1.928		0.1625		0.4835		0.4165						0.7105		0.6315				0.091		0.125		1.5725		0.625		0.0985																														12/20/2002			BASEHIC		AVGAVB				JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.01
Nitrous oxide withdrawal handling induced convulsion (HIC) area under curve		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		02	100 days			Male			5.68		13.24		6.85		1.17		15.6		4.57		5.35		20				2.2		10.15		2.55		1		1.33		3.8						8.87		3.36				6.5		6.67		9		6.94		5.62																														12/20/2002			N2OHIC(AUC)		NCOAUC	Nitrous Oxide	gas 75%	 	JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.02
Corrected peak for nitrous oxide withdrawal handling induced convulsions HIC		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet                                                                                     	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		03	100 days			Male			1.4	0.19	2.94	0.20	1.41	0.25	0.44	0.11	3.4	0.35	1.28	0.27	1.31	0.19	4.17	0.23			0.62	0.19	2.2	0.22	0.88	0.24	0.3	0.13	0.39	0.09	0.73	0.11					2.09	0.36	0.79	0.22			1.71	0.32	1.56	0.28	2	0.31	1.35	0.29	1.35	0.30																													12/20/2002			N2OHIC(PK)		NCORPK2	Nitrous Oxide	gas 75%		JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.03
Nitrous oxide withdrawal handling induced convulsions-difference from baseline (treated minus nontreated)		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet 	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		04	100 days			Male			6.06666666666667		12.635		9.53333333333333		0.333333333333333		14.13		4.25		7.81666666666667		15.977				0.806666666666667		8.35		2.47166666666667		0.55		1.04666666666667		3.55						9.33666666666667		4.24333333333333				6.72666666666667		6.44666666666667		7.21333333333333		9.13666666666667		5.57																														12/20/2002			N2OHIC(DIFF)		NDIFFAUC	Nitrous Oxide	gas 75%		JKB		MRG 011002; prior confirmation by JKB with data and publication	8512534.04
Acute ethanol withdrawal-difference from saline,  [Unpublished means from same series of studies as reported in:  Belknap, Metten, Helms, O'Toole, Angeli-Gade, Crabbe & Phillips, 1993 Behav Genetics 23:213-222]		Recombinant inbred (RI) mouse strains were developed primarily as a tool to detect and provisionally map major gene loci--those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More recently, QTL (quantitative trait loci) approaches have been advanced that do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degree of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to drug abuse and presents new data for studies now in progress for nitrous oxide and acute ethanol withdrawal intensity. These two studies exemplify several strengths and limitations of the RI QTL approach.	Belknap JK, Metten P, Helms ML, O'Toole LA, Angeli-Gade S, Crabbe JC, Phillips TJ.	Quantitative trait loci (QTL) applications to substances of abuse: physical dependence studies with nitrous oxide and ethanol in BXD mice	Behav Genet	23(2)	213-222	Mar	1993 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8512534&dopt=Abstract	8512534		05	100 days			Male			5.227		14.08		8.6		9.303		7.9		1.91		3.05		6.27				1.78		5.07		5.6		3.11		6.3		4.06						8.47		5.707				2.21		6.047		6.696		5.5		1.49																														12/20/2002			ETHIC4(DIFF)		DAUC412	EtOH	4 g/kg		JKB		MRG 020402 with JKB	8512534.05
Home cage activity after saline injection		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	01	10-14 wks	70	98	MF	8		13.25		8.375		11.75		8.625		10.75		15.5		11.25		11.375		8.375		7.88888888888889		6		10.75		8		11.875		10.5		12				7.5		11.375		15.75		1.77777777777778		17.125		11.5		7.5		13.5		9.125		8.625		20.75																								6/4/2003	MK Sullivan		SALACT(Home)		ACT0	Saline	Saline	JKBQTL2	JKB	p. 752, Fig 6	MRG 011002 with JKB by publication	8987796.01
Activity-difference from saline for 4 mg/kg methamphetamine [quadrant crossings/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	02	10-14 wks	70	98	MF	8	quadrant crossings/min	21.625	2.35	18.7678571428571	4.74	47.25	6.70	35.9305555555556	4.39	41.5	7.43	19.25	8.96	7	5.83	33.125	5.26	8.5	2.54	31.8986111111111	3.39	19.875	3.30	13.125	2.96	35.75	6.70	18.125	8.87	21.875	6.26	31.5	6.26			34.375	4.30	9.5	4.74	10.125	5.52	13.8472222222222	4.17	15.5	7.17	22	6.13	25.5	5.39	33.75	4.65	10.375	5.65	30	4.09	14.75	4.09																							6/4/2003	MK Sullivan		MAACT4		DACT4	Meth	4 mg/kg		JKB	p. 748, Fig 2	MRG 011002 with JKB by publication	8987796.02
Activity-difference from saline for 8 mg/kg methamphetamine [quadrant crossings/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	03	10-14 wks	70	98	MF	8	quadrant crossings/min	11.375	3.61	17	5.61	49.875	7.61	24.4861111111111	4.26	43.125	6.70	1.7	5.04	7.25	4.52	14.25	5.78	6.125	4.87	27.4861111111111	3.73	31.5	1.96	15.25	5.13	16.25	7.78	4.375	2.30	16.5	4.43	26.125	8.52			28.7857142857143	4.13	5.5	3.00	-0.875	3.30	25.3472222222222	5.57	9.375	4.17	40.625	7.65	11.5	4.83	12.125	5.57	23.4305555555556	8.96	37.375	4.78	7.375	3.13																							6/4/2003	MK Sullivan		MAACT8		DACT8	Meth	8 mg/kg		JKB	p. 748, Fig 2	MRG 011002 with JKB by publication	8987796.03
Activity-difference from saline for 16 mg/kg methamphetamine [quadrant crossings/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	04	10-14 wks	70	98	MF	8	quadrant crossings/min	-8.75	1.89	3.79166666666667	3.96	6.625	9.96	-0.874999999999998	2.39	8.25	4.89	-12.75	1.88	-9.13888888888889	1.14	-2	3.18	-5.75	1.89	-2.88888888888889	3.22	6.875	5.25	3.625	4.89	-7.14285714285714	0.86	-2	3.07	4.875	6.25	-6.85714285714286	1.61			-1.75	2.14	-4.125	3.64	-7.25	2.86	25.4444444444444	4.75	-13.3472222222222	1.64	8	6.75	-1.75	2.46	-7.7	1.57	11.25	3.86	4.25	2.71	-4.25	5.75																							6/4/2003	MK Sullivan		MAACT16		DACT16	Meth	16 mg/kg		JKB	p. 748, Fig 2	MRG 011002 with JKB by publication	8987796.04
Sterotyped chewing responses [N/min]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	05	10-14 wks	70	98	MF	8	N/min	2.25	0.723	8.375	2.349	0	0.400	1.88888888888889	0.979	1.375	1.396	7.3	1.557	8.25	1.830	5.75	2.323	4.875	1.328	5.04166666666667	2.604	0.125	0.145	2.22222222222222	1.149	9.625	2.162	0.875	0.689	4.5	1.430	7.375	2.545			1.44642857142857	0.987	2.875	2.774	3.375	1.174	1.40277777777778	1.277	0	0.289	3.875	2.026	2.275	1.098	2.125	1.226	0.0833333333333333	0.289	2.125	2.145	-0.125	0.366																							6/4/2003	MK Sullivan		MACHEW8		DCHEW8	Meth	8 mg/kg		JKB	p. 748, Fig 3	MRG 011002 with JKB by publication	8987796.05
Change in body temp due to 4 mg/kg methamphetamine [degree C]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	06	10-14 wks	70	98	MF	8	degree C	0.0124999999999957	0.186	-1.00357142857143	0.536	0.832142857142856	0.345	-0.461111111111116	0.299	0.237500000000004	0.206	-3.72499999999999	0.423	-2.05	0.747	0.424999999999997	0.500	0.0625	0.232	0.588888888888889	0.268	-0.18035714285714	0.232	-1.56250000000001	0.742	0.550000000000004	0.495	-1.2125	0.495	0.362499999999997	0.147	-0.137500000000003	0.711			-1.4375	0.232	-0.487499999999997	0.418	-1.8375	0.820	-1.35277777777779	0.340	-0.275000000000006	0.323	-0.737499999999997	0.325	-1.53750000000001	0.691	-0.537500000000001	0.742	-0.279166666666676	0.299	0.125	0.178	-0.76250000000001	0.289																							6/4/2003	MK Sullivan		MATEMP4		DTEMP4	Meth	4 mg/kg		JKB	p. 747, Fig 1	MRG 011002 with JKB by publication	8987796.06
Change in body temp due to 8 mg/kg methamphetamine [degree C]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	07	10-14 wks	70	98	MF	8	degree C	-0.337499999999991	0.254	-0.0875000000000057	0.207	1.3	0.236	0.294444444444444	0.406	0.674999999999997	0.196	-2.3	0.703	-0.762499999999996	0.283	1.1875	0.120	0.225000000000001	0.330	1.02638888888889	0.232	0.357142857142861	0.286	0.799999999999997	0.351	1.77500000000001	0.196	-1.1125	0.083	1.2375	0.402	0.424999999999997	0.283			0.253571428571433	0.428	0.0124999999999957	0.141	-0.63750000000001	0.630	-0.06527777777778	0.601	-0.125000000000007	0.457	0.525000000000006	0.312	-0.850000000000001	0.580	1.3	0.525	-1.26805555555557	0.359	0.824999999999996	0.170	-0.362500000000004	0.417																							6/4/2003	MK Sullivan		MATEMP8		DTEMP8	Meth	8 mg/kg		JKB	p. 747, Fig 1	MRG 011002 with JKB by publication	8987796.07
Change in body temp due to 16 mg/kg methamphetamine [degree C]		Individual differences in most behavioral and pharmacological responses to abused drugs are dependent on both genetic and environmental factors. The genetic influences on the complex phenotypes related to drug abuse have been difficult to study using classical genetic analyses. Quantitative trait locus (QTL) mapping is a method that has been used successfully to examine genetic contributions to some of these traits by correlating allelic variation in polymorphic genetic markers of known chromosomal location with variation in drug-response phenotypes. We evaluated several behavioral responses to multiple doses of methamphetamine (METH) in C57BL/6J (B6), DBA/2J (D2), and 25 of their recombinant inbred (BXD RI) strains. Stereotyped chewing, horizontal home cage activity, and changes in body temperature after 0, 4, 8, or 16 mg/kg METH, as well as stereotyped climbing behavior after 16 mg/kg METH, were examined. Associations (p < 0.01) between METH sensitivity and allelic status at multiple microsatellite genetic markers were subsequently determined for each response. QTLs were provisionally identified for each phenotype, some unique to a particular behavior and others that appeared to influence multiple phenotypes. Candidate genes suggested by these analyses included several that mapped near genes relevant for the neurotransmitters acetylcholine and glutamate. The locations of QTLs provisionally identified by this analysis were compared with QTLs hypothesized in other studies to influence methamphetamine- and cocaine-related phenotypes. In several instances, QTLs appeared to overlap, which is consistent with idea that common neural substrates underlie some responses to psychostimulants.	Grisel JE, Belknap JK, O'Toole LA, Helms ML, Wenger CD, Crabbe JC. 	Quantitative trait loci affecting methamphetamine responses in BXD recombinant inbred mouse strains	J Neurosci 	17(2)	745-754	Jan	1997		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8987796&dopt=Abstract	8987796	98007483	08	10-14 wks	70	98	MF	8	degree C	0.162500000000001	0.296	0.258333333333326	0.396	1.05	0.217	1.5375	0.316	1.09499999999999	0.316	-0.149999999999991	0.352	0.680555555555557	0.299	1.40000000000001	0.211	0.75	0.316	1.05138888888889	0.228	0.43214285714285	0.168	0.887499999999996	0.177	1.13035714285714	0.493	1.1875	0.524	1.2625	0.382	1.39821428571428	0.234			1.05	0.359	0.325000000000003	0.239	1.1375	0.274	0.377777777777773	0.353	0.791666666666664	0.217	0.725000000000001	0.328	1.2	0.504	2.3525	0.091	-0.100000000000009	0.202	1.2375	0.316	1.01249999999999	0.140																							6/4/2003	MK Sullivan		MATEMP16		DTEMP16	Meth	16 mg/kg		JKB	p. 747, Fig 1	MRG 011002 with JKB by publication	8987796.08
Morphine consumption-two bottle choice [morphine concentration 0.3 to 0.7 mg/ml]		The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		01				Male			157		16		16		42		84		50		27		27				97		29		23		148		16		17						19		96		19		99		52		71		49		97																														12/20/2002			MORCONS		MORCON	Morphine	mg/kg/day		JKB	p. 80, Table 1	MRG 020402 with JKB by publication	2065120.01
Quinine consumption-two bottle choice [quinine concentration 0.1 to 0.4 mg/ml]		The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		02				Male			36		24		32		12		135		20		13		10				11		17		17		62		5		27						11		9		19		58		85		25		39		88																														12/20/2002			QUINCONS		QUINCON	Quinine	mg/kg/day		JKB	p. 80, Table 1	MRG 020402 with JKB by publication	2065120.02
Saccharin preference 	Saccharin preference - mean of 2 studies;Unpublished means from same series of studies as reported in:  1) Phillips, Belknap, Crabbe 1991, J Addictive Diseases 10:73-87;  2) Belknap, Metten, Helms, O'toole, Angeli-Gade, Crabbe & Phillips, 1993 Behav Genetics 23:213-222	The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		97				Male			0.95		0.715		0.79		0.765		0.915		0.9		0.715		0.695				0.765		0.6675		0.805		0.86		0.77		0.765						0.615		0.641		0.84		0.8965		0.717		0.7255		0.873		0.79																														12/19/2002			SACCPREF		SACCPREF	Saccharin	preference ratio		JKB		MRG 020402 with JKB	2065120.97
Saccharin consumption 	Saccharin consumption - mean of 2 studiesUnpublished means from same series of studies as reported in:  1) Phillips, Belknap, Crabbe 1991, J Addictive Diseases 10:73-87;  2) Belknap, Metten, Helms, O'Toole, Angeli-Gade, Crabbe & Phillips, 1993 Behav Genetics 23:213-222	The use of Recombinant Inbred mouse Strains (RIS) to derive information about the complexity of the genetic architecture underlying various traits is increasing in popularity. Behaviors measured to index sensitivity to drug effects and vulnerability to drug abuse are considered here. Potential uses of RIS are identification of major gene effects, mapping of traits to particular chromosomal sites, determining genetic correlations between characters, and identifying behaviorally extreme genotypes. This approach has led to identification of a major gene moderating alcohol acceptance in mice and has revealed a more complex polygenic system influencing morphine consumption.	Phillips TJ, Belknap JK, Crabbe JC.	Use of recombinant inbred strains to assess vulnerability to drug abuse at the genetic level	J Addict Dis 	10(1-2)	73-87		1991		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2065120&dopt=Abstract	2065120		96				Male			806.5		383		352		459.5		1178.5		544.5		342		343				410.5		258.5		528		484		353.5		410						332.5		261.5		417.5		442.5		453.5		365		472		536.5																														12/19/2002			SACCONS		SACCCON	Saccharin	mg/kg/day		JKB		MRG 020402 with JKB	2065120.96
Locomotor activity post cocaine (32 mg/kg) [activity counts/hr]		The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.	Tolliver BK, Belknap JK, Woods WE, Carney JM.	Genetic analysis of sensitization and tolerance to cocaine	J Pharmacol Exp Ther	270(3)	1230-1238	Sep	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7932176&dopt=Abstract	7932176		01				Male	3-8	activitycounts/hr 	1481	89.0	2470	210.3					1814	239.1			2574	251.7			1557	134.3			1622	83.0	1333	69.4	1995	217.4	1787	73.8							2345	83.3	1702	88.7	1383	165.4			2158	112.0	1539	129.6	1494	189.3			1771	117.6	1597	115.8	1909	166.4																							6/26/2003	MK Sullivan		COCACT32		COACT	Cocaine	32 mg/kg		Tolliver/JKB	p. 1235, Fig 6	MRG 011002 with JKB by publication	7932176.01
Sensitization of locomotor response to cocaine (32 mg/kg) [% initial response]		The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.	Tolliver BK, Belknap JK, Woods WE, Carney JM.	Genetic analysis of sensitization and tolerance to cocaine	J Pharmacol Exp Ther	270(3)	1230-1238	Sep	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7932176&dopt=Abstract	7932176		02				Male	3-8	% initial response	81.4		28.2						92.5				71.7				111.4				128.7		97.1		53.1		115.0								59		81.3		100				87.4		86.4		102.0				102		88.6		90																								6/26/2003	MK Sullivan		COCSEN32		COSENSIT	Cocaine	32 mg/kg		Tolliver/JKB	p. 1235, Fig 6	MRG 011002 with JKB by publication	7932176.02
Body weight [g]		Adult C57BL/6J (B6) male mice had 37% heavier brains than did DBA/2J (D2) mice, while their body weights did not differ. The BXD recombinant inbred (RI) series of 20 strains, derived from a cross between B6 and D2 inbred strains, was used as the initial screen to determine significant associations between male brain weight and brain:body weight ratio, with allelic variation at 360 known marker gene loci. For brain weight, this yielded five candidate chromosome regions, each reflecting a possible quantitative trait locus (QTL) site affecting brain weight. The second step was to test as many of these five as possible using standard (non-RI) inbred strain data for brain weight previously reported in the literature. For this purpose, only strains possessing the same alleles as the B6 or D2 strains were used. Sufficient data to test two of the five candidate QTL were available. Of these, one was strongly supported as a site affecting brain weight--the D7rp2 region of chromosome 7. For the brain to body weight ratio, four chromosome regions emerged as significantly associated in the BXD series, but none were amenable to testing due to a lack of allelic information for the standard inbred strains. However, two of these regions showed highly significant associations (p less than 0.001, single test) that merit consideration as QTL sites for future testing. These two are the Hba region on chromosome 11 and the D17Tu7 region on chromosome 17. The genetic correlation between brain and body weight was low (r = 0.28), indicating that these two traits are largely genetically independent in the BXD RI series.	Belknap JK, Phillips TJ, O'Toole LA.	Quantitative trait loci associated with brain weight in the BXD/Ty recombinant inbred mouse strains	Brain Res Bul 	29(3-4)	337-344	Sept-Oct	1992		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1393606&dopt=Abstract	1393606		01	11-13 wks	77	91	Male	7-8	g	25.5	1.71	25.5	2.08	27.6	1.60	28.4	1.84	26.1	1.84	25	2.00	26.4	1.25	27.1	1.64			25.2	0.96	29.3	1.75	30.4	1.60	27.8	1.54	26.75	1.91	29	2.56					28.4	3.26	25.1	0.79	24.3	2.42	25	1.66	24.7	2.17	25.2	2.06	26.3	1.83	24.7	2.23																													6/24/2003	MK Sullivan		BODYWGT		BODWGT			BODYWGT	JKB	p. 340, Table 1	MRG 011002 with JKB by publication	1393606.01
Brain weight [mg]		Adult C57BL/6J (B6) male mice had 37% heavier brains than did DBA/2J (D2) mice, while their body weights did not differ. The BXD recombinant inbred (RI) series of 20 strains, derived from a cross between B6 and D2 inbred strains, was used as the initial screen to determine significant associations between male brain weight and brain:body weight ratio, with allelic variation at 360 known marker gene loci. For brain weight, this yielded five candidate chromosome regions, each reflecting a possible quantitative trait locus (QTL) site affecting brain weight. The second step was to test as many of these five as possible using standard (non-RI) inbred strain data for brain weight previously reported in the literature. For this purpose, only strains possessing the same alleles as the B6 or D2 strains were used. Sufficient data to test two of the five candidate QTL were available. Of these, one was strongly supported as a site affecting brain weight--the D7rp2 region of chromosome 7. For the brain to body weight ratio, four chromosome regions emerged as significantly associated in the BXD series, but none were amenable to testing due to a lack of allelic information for the standard inbred strains. However, two of these regions showed highly significant associations (p less than 0.001, single test) that merit consideration as QTL sites for future testing. These two are the Hba region on chromosome 11 and the D17Tu7 region on chromosome 17. The genetic correlation between brain and body weight was low (r = 0.28), indicating that these two traits are largely genetically independent in the BXD RI series.	Belknap JK, Phillips TJ, O'Toole LA.	Quantitative trait loci associated with brain weight in the BXD/Ty recombinant inbred mouse strains	Brain Res Bul 	29(3-4)	337-344	Sept-Oct	1992		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1393606&dopt=Abstract	1393606		02	11-13 wks	77	91	Male	7-8	mg	465	23	339	19	450	22	390	19	477	27	361	16	421	13	419	15			412	13	403	9	439	9	429	14	436	16	427	13					409	20	431	10	432	30	380	17	394	16	381	18	389	20	375	11																													6/24/2003	MK Sullivan		BRAINWGT		BRAINWGT			BRAINWGT	JKB	p. 340, Table 1	MRG 011002 with JKB by publication	1393606.02
Cocaine in mg/kg (infused via tail vein) to   induce tonic seizure  [mg/kg]		Seizures are a well known consequence of human cocaine abuse, and in rodent models, sensitivity to cocaine seizures has been shown to be strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. This prompted our use of the BXD recombinant inbred (RI) strain set and an F(2) population derived from the B6 and D2 progenitor strains for further genetic analyses and for gene mapping efforts in this study. Cocaine was infused into the lateral tail vein, and the doses needed to induce a running bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. In the BXD RI set, a genome-wide search was carried out for QTLs (quantitative trait loci), which are sites on a chromosome containing genes that influence seizure susceptibility. An F(2) population (B6D2F2, n = 408) was subsequently used as a second, confirmation step. Based on both RI and F(2) results, three QTLs emerged as significant (P <.00005): one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive (P <.0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males.	Hain HS, Crabbe JC,       Bergeson SE, Belknap JK. 	Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains	J Pharmacol Exp Ther	293(1)	180-187	Apr	2000		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10734168&dopt=Abstract	10734168		01	56-100 days 	56	100	Female	7-16	mg/kg	36.5092843340253	1.05	45.8623787362414	1.15	42.9703626911218	1.99	46.3609349736889	1.81	43.4960099553144	3.05	48.0771280463759	2.93	44.6149206926665	2.06	38.9730137289765	1.64	48.6677557555129	1.60	39.5212449334861	1.03	39.4036744928305	1.27	39.9767680020278	1.74	37.3012008962622	1.55	43.3300328369933	1.78	39.4037704331372	1.18	45.4332262655791	1.24			35.9427625388382	1.01	49.5509290179926	2.94			38.7927845701966	1.48	46.6208980595439	3.05	38.7701207182665	1.08	38.7466553026451	1.64	44.3891465498985	2.56	42.0057332089545	1.24	34.0522375511561	0.70	44.0018244149537	1.59																							6/4/2003	MK Sullivan	MK Sullivan	COCTON		MGKGTON	Cocaine	1mg/ml	RI-166	JKB/JCC	p. 182, Fig.1 top	JD 121301  from publication	10734168.01
Cocaine in mg/kg (infused via tail vein) to induce clonic seizure [mg/kg]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            		Seizures are a well known consequence of human cocaine abuse, and in rodent models, sensitivity to cocaine seizures has been shown to be strongly influenced by genotype. For example, several studies have reported significant differences between the C57BL/6 (B6) and DBA/2 (D2) inbred mouse strains in their sensitivity to cocaine-induced seizures. This prompted our use of the BXD recombinant inbred (RI) strain set and an F(2) population derived from the B6 and D2 progenitor strains for further genetic analyses and for gene mapping efforts in this study. Cocaine was infused into the lateral tail vein, and the doses needed to induce a running bouncing clonic seizure and a tonic hindlimb extensor seizure were recorded for each mouse. In the BXD RI set, a genome-wide search was carried out for QTLs (quantitative trait loci), which are sites on a chromosome containing genes that influence seizure susceptibility. An F(2) population (B6D2F2, n = 408) was subsequently used as a second, confirmation step. Based on both RI and F(2) results, three QTLs emerged as significant (P <.00005): one for clonic seizures on chromosome 9 (distal), and two for tonic seizures on chromosomes 14 (proximal to mid) and 15 (distal). Two additional QTLs emerged as suggestive (P <.0015), both associated with clonic seizures on chromosomes 9 (proximal) and 15 (distal). Both QTLs on chromosome 9 were sex-specific, with much larger effects on the phenotype seen in females than in males.	Hain HS, Crabbe JC,  Bergeson SE, Belknap JK. 	Cocaine-induced seizure thresholds: quantitative trait loci detection and mapping in two populations derived from the C57BL/6 and DBA/2 mouse strains	J Pharmacol Exp Ther	293(1)	180-187	Apr	2000		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10734168&dopt=Abstract	10734168		02	56-100 days 	56	100	Female	7-16	mg/kg	21.1275869781027	0.75	21.903677521797	1.59	24.3794503374416	3.26	21.8333066738383	2.18	21.6786293001535	2.46	20.1582397852819	1.24	23.9731186492713	1.45	21.8606255012244	1.83	24.867635937228	1.55	17.5034216551746	1.22	21.7689514914138	0.99	21.8178716923466	1.76	17.4457084496112	1.71	20.1131869961416	1.18	24.3516411928639	1.45	23.4871948042632	1.45			20.3500609275227	1.01	23.5815221713196	2.51			20.7144960755053	1.72	22.1648480352814	2.23	22.8863072036995	1.95	19.6430463704733	1.43	20.8623671215829	1.66	22.8056520761417	1.66	20.1509430417039	1.20	20.7370448138035	0.98																							6/4/2003	MK Sullivan	MK Sullivan           	COCCLO		MGKGCLO	Cocaine	1mg/ml	RI-166	JKB/JCC	p. 182, Fig.1 bottom	JD 121301  from publication	10734168.02
Acute ethanol activity response - Difference between experimental 2g/kg ip EtOH and saline control group [activity counts/min]		Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL 	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	01	56-125 days	56	125	Male	13-34	activity counts/min	28.869	8.34	75.200	8.27	42.207	8.30	20.144	4.90	36.412	2.44	15.49	3.92	85.832	4.97	49.069	4.57	52.4	6.92	2.147	4.90	43.093	4.50	58.071	6.34	18.172	2.91	15.048	2.78	44.434	7.15					50.538	5.53	33.052	5.00			28.221	3.84	68.007	9.87	38.566	10.60	23.353	4.77	31.488	5.05																													7/3/2003	MK Sullivan		ETSALACT(C1DIFF)	Figure 1 data; also EtOH: Act in Tables 4-5	E1MS1; C1	EtOH	2 g/kg	CPP-59	CLC	Fig 1; Tables 4-5	MRG 120601 from publication	7480533.01
Within-subject tolerance/sensitization to ethanol effects on locomotor activity (i.e., 4th ethanol trial activity minus 1st ethanol trial activity)		Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology 	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	02	56-125 days	56	125	Male			-59.094		26.921		-44.237		-26.048		-22.375		-47.387		-10.206		15.869		-37.031		-23.027		-19.28		-30.107		-15.159		-29.042		-1.931						10.117		-2.704				7.3		-34.855		34.772		-15.973		-4.218																														12/20/2002			ETSEN (C4C1)	SENS1: ACT	E4ME1	EtOH	2 g/kg	CPP-59	CLC	means not in paper; analyzed in Tables 4-5	MRG 120601 from publication	7480533.02
Ethanol induced conditioned place preference - Time on EtOH paired floor during 30 min test [%]		Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL 	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	03	56-125 days	56	125	Male	6-16	%	58.316	2.38	59.618	3.38	65.087	3.56	62.43	3.56	54.588	2.58	63.214	2.80	59.001	2.26	60.163	2.01	78.344	3.80	57.973	2.87	59.701	2.74	55.239	2.54	64.039	2.92	61.564	5.14	57.696	1.98					49.491	1.80	65.529	5.04			74.6	3.32	49.865	2.18	66.859	4.08	54.526	3.50	53.349	1.99																													7/2/2003	MK Sullivan		ETCPP	PREF	PDT30	EtOH	2 g/kg	CPP-59	CLC	p. 33, Fig 2	JD 010302 from publication	7480533.03
Within-subject habituation (i.e., 4th saline trial activity minus 1st saline activity trial activity)	[Unpublished means from same series of studies as reported in:    Cunningham 1995 PsychoPharm 120:28-41]	Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.	Cunningham CL	Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice	Psychopharmacology	120(1)	28-41	July	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7480533&dopt=Abstract	7480533	96078685	95	56-125 days	56	125	Male			-47.925		-10.243		-37.8		-36.568		-13.088		-41.865		-18.465		-20.793		-21.569		-32.167		-22.473		-23.9		-8.386		-17.503		-14.676						-6.034		-11.252				-6.357		-32.848		-26.041		-14.067		-18.888																														12/19/2002			SALACT(C4C1)		S4MS1	Saline		CPP-59	CLC		JD 010302 from publication	7480533.95
Acute Locomotor Activity Response to 2 g/kg i.p. EtOH on 11th day in chronic saline injected mice, 1- 5 minutes after injection [cm]		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	01	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	546		973		-241		725		-208		-493		1185		358		921		387		662		813		-266		38		726						1074		454		996		194		1242		837		529		309																														12/27/2002			ETACT2(CS)	ACCS	CS5D11D2	EtOH	2 g/kg	RI-58	TJP	Figure 1 inset y-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.01
Ethanol Locomotor Sensitization Between Group: Acute Response to 2 g/kg EtOH, Day 11 Locomotor Activity Difference (Chronic EtOH minus Chronic Saline), 1-5 minutes after injection [cm] 		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	02	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	-694		-134		-468		507		435		395		-558		663		456		-372		1226		275		176		1026		1065						696		-62		758		935		430		388		677		356																														12/27/2002			ETSEN2(BG)	deltaBG	BGSENS5M	EtOH	2 g/kg	RI-58	TJP	Figure 2 inset y-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.02
Ethanol Locomotor Sensitization Within Group: Change in locomotor response, 1 - 5 minutes after 2 g/kg EtOH injection (i.p) after repeated treatment; Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) for the chronic EtOH group [cm]		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	03	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	-318	124	-725	350	-866	200	260	289	279	117	-51	223	-1013	488	1060	303	726	492	-297	303	644	309	-46	231	365	188	433	242	1119	309					682	427	39	242	1125	293	899	175	252	203	402	270	586	298	192	266																													7/2/2003	MK Sullivan		ETSEN2(CD)	deltaCD	D11D35M	EtOH	2 g/kg	RI-58	TJP	Figure 2 and Figure 2 inset x-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.03
Acute locomotor response, 1 to 5 minutes after 2g/kg i.p. EtOH in chronic ethanol sensitized mice [cm] 		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	04	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	84	114	1521	263	268	265	843	100	-174	95	-36	138	1587	358	-162	174	924	396	504	168	976	200	1157	243	-204	121	649	159	675	187					1026	284	163	124	644	210	45	87	1445	189	891	181	747	193	382	143																													7/2/2003	MK Sullivan		ETACT2(CD)	ACCD	D3D25M	EtOH	2 g/kg	RI-58	TJP	Figure 1 and Figure 1 inset x-axis, p. 273	MRG 010202 with TJP from publication and data file	7625557.04
Locomotor Activity Day 2, 1 - 5 minutes after saline i.p. [cm]		Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, i.p) exposures were measured in BXD recombinant inbred (RI) mice and their C57BL/6J (B6) and DBA/2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulant/sensitizing effects of EtOH and EtOH consumption.	Phillips TJ, Huson M, Gwiazdon C, Burkhart-Kasch S, Shen EH.	Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice	Alcohol Clin Exp Res	19(2)	269-278.	Apr	1995 		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7625557&dopt=Abstract	7625557	95351511	05	7-19 wks	49	133	Female		Horizontal Distance traveled cm 	1447		1362		1661		1528		1086		1162		886		1845		573		1643		1175		1729		1171		1035		2014						1411		949		1264		823		1360		1074		899		2146																														12/27/2002			SALACT(5MIN)	BASACT5	SAL5M	Saline		RI-58	TJP	Basis for QTL analysis of basal activity, p. 272 Table 2	MRG 010202 with TJP from publication and data file	7625557.05
Consumption of 0.2% saccharin (mg/kg) vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		01	51-125 days	51	125	Female	10-18	g/kg/day	853.935	111.717	471.707	73.838			250.743	80.303	748.408	168.939	787.394	43.939			330.42	58.485			343.077	57.980	420.033	54.495	537.171	90.909	652.835	72.576	415.414	47.879	412.785	59.596	639.584	75.253			533.912	23.333			438.621	105.001	674.217	92.980	807.822	70.152	534.837	58.434			1071.038	88.637			591.661	116.768	572.167	55.012																							7/11/2003	MK Sullivan		SACCONS0.2(%)	0.2%SacCon	AVSACCON	Saccharin	0.002	RI-72	TJP	p. 935, Fig. 2	MRG 010202 with TJP from publication and data file	7978106.01
Consumption of 3% Ethanol (g/kg) vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		02	51-125 days	51	125	Female	10-18	g/kg/day	3.538	0.557	0.279	0.264			2.052	0.841	1.669	0.734	2.086	0.417			0.981	0.301			2.765	0.446	0.438	0.286	0.906	0.374	3.578	0.657	2.218	0.539	0.951	0.341	2.975	0.403			0.967	0.516			1.64	0.786	0.614	0.246	1.741	0.551	2.159	0.821			2.795	0.517			2.658	0.601	0.819	0.429																							7/11/2003	MK Sullivan		ETCONS3(%)	3%EtOHCon	AV3EG	EtOH	0.03	RI-72	TJP	p. 934, Fig.1	MRG 010202 with TJP from publication and data file	7978106.02
Consumption of 3% Ethanol (g/kg) in 0.2% saccharin vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		03	51-125 days	51	125	Female	10-18	g/kg/day	10.965	0.635	2.000	0.721			6.135	0.833	11.207	1.051	7.023	0.829			2.924	0.633			4.828	0.424	6.245	1.666	6.159	0.945	7.236	0.875	5.58	0.563	3.274	0.845	5.534	0.614			5.473	0.547			11.658	0.719	6.992	0.630	8.083	0.547	6.646	0.766			10.266	0.896			7.308	1.060	4.638	0.980																							7/11/2003	MK Sullivan		ETSACCONS3(%)	3%EtOH/SacCon	AV3SG	EtOH	0.03	RI-72	TJP	p. 935, Fig. 2	MRG 010202 with TJP from publication and data file	7978106.03
Consumption of 10% Ethanol (g/kg) in tap water offered vs. tap water; means are the average of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		04	51-125 days	51	125	Female	10-18	g/kg/day	10.562	1.319	1.306	0.981			6.084	1.505	5.506	1.192	4.425	1.008			0.601	0.012			2.759	0.918	0.687	0.411	1.741	0.613	5.836	1.210	4.849	1.407	0.364	0.105	2.477	0.916			2.589	1.017			2.203	1.032	2.417	0.805	2.024	0.706	6.658	0.903			2.466	0.901			8.096	1.403	1.28	0.905																							7/11/2003	MK Sullivan		ETCONS10(%)	10%EtOHCon	AV10EG	EtOH	0.1	RI-72	TJP	p. 934, Fig.1	MRG 010202 with TJP from publication and data file	7978106.04
Consumption of 10% Ethanol (g/kg) in 0.2% saccharin and tap water offered vs. tap water; means of days 2 and 4 of a 4-day 24-hr access period [g/kg/day]		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		05	51-125 days	51	125	Female	10-18	g/kg/day	18.194	1.847	1.05	0.660			11.378	1.216	13.58	1.435	12.161	1.241			1.98	0.637			6.256	1.020	6.588	2.212	5.727	1.120	14.376	0.540	11.1	1.626	3.678	1.112	6.692	1.543			8.083	1.528			15.58	1.78	10.256	0.747	10.05	0.235	12.975	1.642			13.02	1.740			12.737	0.871	4.135	1.568																							7/11/2003	MK Sullivan		ETSACCONS10(%)	10%EtOH/SacCon	AV10SG	EtOH	0.1	RI-72	TJP	p. 935, Fig. 2	MRG 010202 with TJP from publication and data file	7978106.05
Corrected area under the Ethanol withdrawal curve; mice were assessed for handling-induced convulsions after voluntary ethanol consumption.		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		06	51-125 days	51	125	Female	10-18		5.66		2.61				0.52		2.18		5.69				0.6				1.64		1.05		1.17		3.21		4.68		0.48		0				4.82				1.26		1.75		2.33		3.3				3.42				0.31		1.5																								12/20/2002			ETHIC	EtOHWD	COAUC	EtOH	0.1	RI-72	TJP	p.938, Table 2	MRG 010202 with TJP from publication and data file	7978106.06
Preference for 10% Ethanol (g/kg) in tap water offered vs. tap water; means are the average of days 2 and 4 of a 4-day 24-hr access period.		The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.	Phillips TJ, Crabbe JC, Metten P, Belknap JK.	Localization of genes affecting alcohol drinking in mice.	Alcohol Clin Exp Res	18(4)	931-941	Aug	1994		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7978106&dopt=Abstract	7978106		07	51-125 days	51	125	Female	10-18		0.554		0.086				0.32		0.35		0.251				0.051				0.168		0.045		0.061		0.356		0.302		0.024		0.167				0.146				0.127		0.265		0.171		0.428				0.14				0.488		0.112																								12/20/2002			ETPREF10(%)	10%EtOHPref	PR10E	EtOH	0.1	RI-72	TJP	p. 934, Fig.1	MRG 010202 with TJP from publication and data file	7978106.07
Locomotor response (photocell beam interruptions) to acute 2 g/kg i.p Ethanol injection; Day 3 (first Ethanol treatment) minus Day 2 (saline baseline) in the chronic EtOH group; 10 min activity test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR. 	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		01				Female			-18		151		96		350		-227		-401		88				188		-128		353		79		78		-67		269		541				562		-117		-37		-44		241		608		-23		58		947		-142		-345																								12/20/2002			ETACT2(GRIDCD)		ACTD3D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 2 top	MRG 010202 with TJP from publication and data file	8627538.01
Locomotor response (photocell beam interruptions) to acute 2 g/kg Ethanol injection (i.p); Day 11 (only Ethanol treatment) minus Day 2 (saline baseline) in the chronic saline (CS) group; 10 min activity test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		02				Female			-105		272		68		304		-426		-443		170				262		33		524		-68		3		-214		213		780				428		8		-23		79		247		687		-30		538		979		-13		-379																								12/20/2002			ETACT2(GRIDCS)		ACTD11D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 2 top inset	MRG 010202 with TJP from publication and data file	8627538.02
Change in locomotor response (photocell beam interruptions) to 2 g/kg i.p EtOH injection (i.p) after repeated treatment; Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) in the chronic drug (CD) group; 10 min activity test (Grid test inside Accuscan activity monitors).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther2	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		03				Female			20		265		164		-238		254		214		121				395		201		516		119		210		386		482		234				136		234		360		98		548		-140		428		982		261		205		466																								12/20/2002			ETSENS2(GRIDCD)		ACTD11D3	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 2 bottom	MRG 010202 with TJP from publication and data file	8627538.03
Acute Ethanol Ataxia: Grid test errors after acute 2 g/kg EtOH injection (i.p); Day 3 (first EtOH treatment) minus Day 2 (saline baseline) in the chronic drug (CD) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		04				Female			114		123		135		187		86		103		143				129		154		191		165		138		227		320		289				186		108		165		132		151		185		152		298		159		164		109																								12/20/2002			ETGRID2(CD)		ERRD3D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 1 top	MRG 010202 with TJP from publication and data file	8627538.04
Acute Ethanol Ataxia: Grid test errors after acute 2 g/kg EtOH injection (i.p); Day 11 (only EtOH treatment) minus Day 2 (saline baseline) in the chronic saline (CS) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		05				Female			116		168		150		199		91		111		201				153		140		230		210		129		195		287		351				175		110		185		106		172		256		130		337		212		171		107																								12/20/2002			ETGRID2(CS)		ERRD11D2	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 1 top inset	MRG 010202 with TJP from publication and data file	8627538.05
Change in misstep errors induced by repeated 2 g/kg EtOH injection (i.p); Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) in the chronic drug (CD) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		06				Female			-33		-40		33		-83		-13		-14		-18				-43		-40		64		-5		-13		-30		83		-34				-33		-10		-8		-69		-7		4		66		-63		-57		-24		47																								12/20/2002			ETGRIDTOL2(CD)		ERRD11D3	EtOH	2 g/kg	RI-82	TJP	p. 616, Fig 1 bottom	MRG 010202 with TJP from publication and data file	8627538.06
Ataxia ratio (errors/activity counts) in the Grid test after acute 2 g/kg Ethanol injection (i.p); Day 3 (first Ethanol treatment) minus Day 2 (saline baseline) in the chronic drug (CD) group; 10 min test (Grid test inside Accuscan activity monitors).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		07				Female			17.6		11.4		14.8		20.8		18.1		25.2		18.5				14.9		17.6		18		19.7		17.7		47.6		26.4		22.9				14.5		19.8		26.3		33.7		14		14.3		24.4		16.9		9		29.9		24																								12/20/2002			ETGRID2 (CD RATIO)		RATD3D2	EtOH	2 g/kg	RI-82	TJP	p. 617, Fig 3 top	MRG 010202 with TJP from publication and data file	8627538.07
Ataxia ratio (errors/activity counts) in the Grid test after acute 2 g/kg Ethanol injection (i.p); Day 11 (only EtOH treatment) minus Day 2 (saline baseline) in the chronic saline (CS) group; 10 min test (Accuscan activity Monitor Grid test).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		08				Female			15.9		14.7		14.3		19.9		26		27.5		22.7				18.2		15.1		18.1		26		17.5		47.5		24.5		24.5				16.1		17.4		27.3		27.1		17.9		18.5		22.1		17.6		11.1		32.7		22.9																								12/20/2002			ETGRID2 (CS RATIO)		RATD11D2	EtOH	2 g/kg	RI-82	TJP	p. 617, Fig 3 top inset	MRG 010202 with TJP from publication and data file	8627538.08
Change in ataxic effects of 2 g/kg Ethanol injection (i.p) after repeated treatment; Day 11 (fifth EtOH treatment) minus Day 3 (first EtOH treatment) in the chronic drug (CD) group; 10 min test (Grid test inside Accuscan activity monitors).		Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.	Phillips TJ, Lessov CN, Harland RD, Mitchell SR.	Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice	J Pharmacol Exp Ther	277(2)	613-623	May	1996		http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8627538&dopt=Abstract	8627538		09				Female			-6.9		-5.1		0.3		-8		-6.8		-11.2		-2.8				-8		-8.2		-1.3		-5.4		-5.3		-23.5		-0.6		-5.3				-3.8		-8.4		-10.2		-22.3		-5.8		0.8		-2.7		-8.6		-4.6		-12.4		-7.5																								12/20/2002			ETGRIDTOL2 (CD RATIO)		RATD11D3	EtOH	2 g/kg	RI-82	TJP	p. 617, Fig 3 bottom	MRG 010202 wi