Localization of genes influencing ethanol-induced conditioned place preference and locomotor activity in BXD recombinant inbred mice

C. L. Cunningham

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

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 ethanolpaired 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.

Original languageEnglish (US)
Pages (from-to)28-41
Number of pages14
JournalPsychopharmacology
Volume120
Issue number1
DOIs
StatePublished - Jul 1995

Keywords

  • Conditioned place preference
  • Ethanol
  • Habituation
  • Locomotor activity
  • Mice
  • Quantitative trait loci
  • Recombinant inbred strains
  • Reinforcement
  • Reward
  • Sensitization
  • Tolerance

ASJC Scopus subject areas

  • Pharmacology

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