Rationale: Results from clinical studies have shown that topiramate effectively reduces alcohol consumption in a population of heavy-drinking alcohol-dependent humans. Objectives: We undertook this preclinical study in order to establish topiramate's efficacy in a rodent model and to determine whether topiramate's efficacy may vary with level of drinking and/or genetic background. Methods: The effects of acutely administered topiramate (0, 5, and 10 mg/kg) on ethanol consumption were examined in a large group of ethanol-preferring (P) rats (N=20) in order to assess the relationship between level of consumption and treatment effect using a two-bottle free-choice paradigm (10% ethanol versus water). We also evaluated the effects of topiramate in two groups of Wistar rats that were given access to ethanol under either the standard two-bottle free-choice paradigm or under conditions that are known to produce higher levels of daily ethanol consumption (i.e. three-bottle free choice). Results: Topiramate treatment produced a modest, but persistent (average of 5 days), reduction in ethanol consumption in P rats, and this effect did not vary with level of consumption. Topiramate did not affect ethanol consumption in either group of Wistar rats. Conclusions: The results from this study establish in a rodent model that topiramate effectively and persistently reduces ethanol consumption and suggests that its efficacy may depend on genetic vulnerability but not level of drinking.
- P rats
- Wistar rats