Role of test activity in ethanol-induced disruption of place preference expression in mice

Rationale Reduced expression of a drug-induced conditioned place preference (CPP) may reflect a decrease in the drug's conditioned rewarding effects. However, CPP is also open to disruption by processes unrelated to the underlying motivation. In unpublished studies, we previously observed that ethanol pretreatment before testing disrupted expression of ethanol-induced CPP in DBA/2J mice. We hypothesized that this interference effect was due to large ethanol-induced increases in activity. Objective The present studies were designed to examine the relationship between test activity and expression of ethanol-induced CPP both in the presence and absence of ethanol. To assess the generality of this relationship, we examined these effects both in DBA/2J (which are highly activated by ethanol) and in NZB/B1NJ mice (which show similar CPP, but less ethanol-induced activation). Materials and methods in separate experiments, inbred mice from each strain underwent ethanol (2 g/kg) place conditioning. Saline or ethanol was then administered immediately before the test. Results Ethanol, given immediately before the test, blocked the expression of ethanol CPP in DBA/2J, but not in NZB/B1NJ mice. Moreover, ethanol significantly increased test activity levels in DBA/2J and to a much lesser degree in NZB/B1NJ mice. Correlation analyses showed an inverse phenotypic relationship between preference and test activity, reflecting stronger preferences in less active mice. Conclusions Disruption of ethanol-CPP observed in DBA/2J mice may be a consequence of high ethanol-induced activity levels. More generally, these studies suggest that competing behaviors can affect expression of a drug-induced CPP independent of affecting the conditioned rewarding effects of the drug.