Short-term selective breeding created mouse lines divergent for ethanol drinking (high drinking short-term selected line [STDRHI], low drinking [STDRLO]) or ethanol-induced conditioned taste aversion (CTA; high [HTA], low [LTA]). Compared with STDRLO, STDRHI mice consumed more saccharin and less quinine, exhibited greater ethanol-induced conditioned place preference (CPP), and showed reduced ethanol stimulation and sensitization under some conditions; a line difference in ethanol-induced CTA was not consistently found. Compared with LTA, HTA mice consumed less ethanol but were similar in saccharin consumption, sensitivity to ethanol-induced CPP, and ethanol-induced locomotor stimulation and sensitization. These data suggest that ethanol drinking is genetically associated with several reward-and aversion-related traits. The interpretation of ethanol-induced CTA as more genetically distinct must be tempered by the inability to test the CTA lines beyond Selection Generation 2.

Genetic differences in sensitivity to cocaine's rewarding effect depend critically on temporal parameters of the place-conditioning procedure. One possible interpretation of these findings is that short trial durations produce conditioned activity responses that interfere more with expression of conditioned place preference in DBA/2J mice than in C57BL/6J mice. More generally, these findings underscore the need for caution when drawing conclusions about genetic differences in place conditioning, especially when using this paradigm to evaluate the effects of gene knockouts or insertions on drug reward.

Previous place conditioning studies in mice have shown that injection of ethanol immediately before a conditioned stimulus (CS+) produces conditioned preference, whereas injection of ethanol immediately after CS+ produces conditioned aversion. In the present experiments, we examined the learning that occurs when ethanol is injected in "ambiguous" procedures that provide the opportunity for both types of conditioning. When ethanol was given midway through the CS (Experiments 1 and 2) or both before and after the CS (Experiment 3), the direction of place conditioning was the same as when mice were exposed only to whichever contingency occurred first (a primacy effect). That is, injection of ethanol in the middle of the CS conditioned aversion, whereas injection both before and after the CS conditioned preference. Because these results support the idea that ethanol elicits both aversive and rewarding effects, they are most consistent with conditioning theories that conceptualize unconditioned stimuli (USs) as events that can activate multiple representational components.