BACKGROUND Topiramate, an anticonvulsant, has been reported to increase the number of abstinent days and decrease craving in alcohol-dependent individuals. However, the neurobiological basis for topiramate's effect is unknown. To assess topiramate's effect on ethanol's rewarding and conditioning rewarding effects, the present experiments examined the effects of topiramate on the acquisition and expression of ethanol-induced conditioned place preference (CPP) in DBA/2J and C57BL/6J mice. METHODS A biased apparatus and subject assignment were used. Mice received ethanol (2 g/kg) or saline paired with an initially nonpreferred floor (CS+) and saline paired with an initially preferred floor (CS-) for 5-minute conditioning trials. During the acquisition experiments, mice received a pretreatment of topiramate (0, 5, 10, 20, 50, or 100 mg/kg) 1 hour before the CS+ trials. On intervening CS- trials, mice received a pretreatment of saline. For the preference test, all mice received saline injections and were placed on a split floor for a 30-minute test. During the expression experiments, mice received no drug pretreatment on conditioning trials, but were pretreated with topiramate (0, 10, 50, or 100 mg/kg) 1 hour before the test session. RESULTS Ethanol-induced CPP was observed in both strains, but topiramate did not affect the acquisition or expression of ethanol-induced CPP in either strain. Despite its failure to alter CPP, topiramate produced dose-dependent locomotor activating effects in both strains. These effects were observed both in the presence and in the absence of ethanol. CONCLUSIONS These findings indicate that topiramate has no effect on ethanol's rewarding or conditioned rewarding effects as indexed by the place conditioning procedure. Thus, these studies raise the possibility that topiramate's efficacy in the treatment of alcoholism results from its impact on brain areas other than those that mediate ethanol's rewarding or conditioned rewarding effects. One alternative possibility is that topiramate decreases withdrawal-induced negative affective states that normally contribute to relapse.