Florence J Breslin1, Bankole A Johnson, Wendy J Lynch. 1. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia Health System, 1670 Discovery Drive, Charlottesville, VA 22911, USA.
Abstract
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.
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.
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