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Psychopharmacology (Berl). 2011 Sep;217(1):3-12. doi: 10.1007/s00213-011-2253-0. Epub 2011 Mar 22.

Severity of drinking as a predictor of efficacy of the combination of ondansetron and topiramate in rat models of ethanol consumption and relapse.

Author information

1
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Charlottesville, VA 22911, USA. wlynch@virginia.edu

Abstract

RATIONALE:

Alcohol dependence is the third leading cause of preventable death in the USA. While single-agent pharmacotherapies have variable efficacy, medication combinations may produce additive effects by modulating multiple neural pathways.

OBJECTIVES:

Here, we examined in animal models of ethanol consumption and relapse the combined effects of ondansetron (a serotonin-3 antagonist) and topiramate (a GABA/glutamate modulator), two medications with demonstrated efficacy for treating alcohol dependence, hypothesizing that their combination would produce a more efficacious response.

METHODS:

The effects of acutely administered ondansetron (0-0.01 mg/kg) and topiramate (0-10 mg/kg) alone and in combination on ethanol consumption were examined in alcohol preferring (P) rats (N = 20) and in rats from their background strain (Wistars, N = 20) using a 24-h access free-choice paradigm. Next, we examined their ability to prevent an increase in ethanol consumption following a deprivation period (i.e., an animal model of relapse).

RESULTS:

Whether administered alone or combined with ondansetron, topiramate produced a similar modest but persistent reduction in ethanol consumption. However, an analysis of efficacy by drinking level revealed that the combination was superior to topiramate alone in heavy-drinking P rats, but was without effect in lighter-drinking P rats and Wistar rats. Both topiramate alone and the combination blocked the alcohol deprivation effect in both Wistar and P rats with the combination tending to produce a greater decrease than topiramate alone.

CONCLUSIONS:

The combination of ondansetron and topiramate may be a promising treatment for preventing relapse and for treating alcohol dependence in heavy-, but not lighter-drinkers.

PMID:
21424693
PMCID:
PMC4086466
DOI:
10.1007/s00213-011-2253-0
[Indexed for MEDLINE]
Free PMC Article

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