title: Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice.
abstract: 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.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005796:Genes / Q000235:genetics*; D006185:Habituation, Psychophysiologic; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D012201:Reward; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D000431:Ethanol; D012965:Sodium Chloride