Effects of multi-modal cues on conditioned place preference in C57BL/6J and DBA/2J mice

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.

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.

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.

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.

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.