Genetic differences in cocaine-induced conditioned place preference in mice depend on conditioning trial duration

Rationale: In previous comparisons with C57BL/6J mice, DBA/2J mice have bee n characterized as "hyporesponsive" to cocaine's rewarding effect in the co nditioned place-preference paradigm. This finding contrasts with other stud ies showing greater sensitivity of DBA/2J mice to the rewarding effects of ethanol and morphine in the place conditioning task. Objectives: The purpos e of the present study was to examine cocaine-induced place conditioning in both strains using apparatus and procedures similar to those used previous ly to assess ethanol and morphine preference conditioning. Methods: Mice fr om both strains were exposed to an unbiased place-conditioning procedure us ing 1, 10, or 30 mg/kg cocaine. Conditioning trial duration was 15, 30, or 60 min. Results: In general, C57BL/6J mice displayed a significant conditio ned place preference that was relatively unaffected by cocaine dose or tria l duration. In contrast, DBA/2J mice showed no place conditioning at the sh ortest trial duration, but an increasing level of preference as trial durat ion increased. At the longest trial duration, both strains showed similar l evels of place preference. Conclusions: Genetic differences in sensitivity to cocaine's rewarding effect depend critically on temporal parameters of t he place-conditioning procedure. One possible interpretation of these findi ngs is that short trial durations produce conditioned activity responses th at 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 plac e conditioning, especially when using this paradigm to evaluate the effects of gene knockouts or insertions on drug reward.