Rationale: Previous work has shown that some mouse strains (e.g., DBA/2J [D2]) readily develop robust ethanol-induced conditioned place preference (CPP) while others (e.g., C57BL/6J [B6]) do not. Though commonly interpreted as a difference between strains in sensitivity to ethanol reward, other explanations for this finding are possible. Objectives: To explore the hypothesis that variation in sensitivity to contextual cues underlies CPP differences, the present work investigated ethanol-induced CPP in D2 and B6 mice trained with a standard tactile (floor) cue procedure compared to mice trained with tactile plus visual-spatial cues. Methods: In an unbiased CPP procedure, mice were assigned to either a single element cue (one-compartment apparatus with tactile cue presented in the dark) or multi-modal cues (two-compartment apparatus with distinct tactile floors and lights on). To track CPP development, mice received preference tests during training in addition to a final test. Results: Adding visual-spatial cues accelerated CPP acquisition in both D2 and B6 mice. However, this enhancement was observed after just one ethanol-conditioning trial in D2 mice, but was observed only after four ethanol-conditioning trials in B6 mice. Differences between groups trained with single or multi-modal cues disappeared as conditioning reached asymptote, with D2 mice showing a more rapid loss of the effect and a higher maximum CPP. Conclusions: Although multi-modal cues produce more rapid conditioning, their inability to reduce or eliminate strain differences in CPP supports the interpretation that these strains differ in their sensitivity to ethanol reward.
- Inbred mice (C57BL/6J
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