Effect of topiramate treatment on ethanol consumption in rats
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Results from clinical studies have shown that topiramate effectively reduces alcohol consumption in a population of heavy-drinking alcohol-dependent humans.
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.
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).
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.
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.
KeywordsAlcohol Consumption Ethanol P rats Wistar rats Topiramate
Acknowledgment of funding and grants
This project was supported by funding from the Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia in Charlottesville, Virginia. The P rats for this study were provided by the Indiana Alcohol Research Center, which is funded by grant 5P50AA007611-159005 from the National Institute on Alcohol Abuse and Alcoholism.
We thank Robert H. Cormier, Jr., BA, for his assistance with manuscript preparation, and Colin Bond for his technical assistance.
The experiments described herein comply with the current laws of the United States of America.
Conflicts of interest
The authors have no potential conflicts of interest pertaining to the subject of this report. In the past 4 years, Prof. Johnson has been a consultant for Ortho-McNeil Janssen Scientific Affairs LLC, Organon, and Transcept Pharmaceuticals Inc. Ms. Breslin and Dr. Lynch have no financial disclosures to report.
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