The efficacy of a low dose combination of topiramate and naltrexone on ethanol reinforcement and consumption in rat models.

Autor: Moore CF; Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States., Protzuk OA; Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States., Johnson BA; Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States., Lynch WJ; Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States. Electronic address: wlynch@virginia.edu.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2014 Jan; Vol. 116, pp. 107-15. Date of Electronic Publication: 2013 Nov 16.
DOI: 10.1016/j.pbb.2013.11.013
Abstrakt: Rationale: Combined medication approaches, by targeting multiple neurotransmitter systems involved in alcohol use disorders (AUDs), may be more efficacious than single-medication approaches.
Objectives: We examined, in animal models of consumption and reinforcement, the combined effects of naltrexone (an opioid antagonist) and topiramate (a GABA/glutamate modulator), two medications that have shown promise for treating AUDs, hypothesizing that their combination would be more efficacious than either alone.
Methods: The effects of naltrexone and topiramate on ethanol consumption were examined in alcohol preferring (P) rats (N=10) and in rats from their background strain (Wistar, N=9) using conditions that induce high levels of consumption (24-h, 3-bottle, free-choice procedure). Low doses of each medication (1mg/kg, naltrexone; 10mg/kg, topiramate) were selected in an attempt to maximize their combined efficacy while minimizing potential side-effects. Their effects on ethanol reinforcement were assessed under a progressive-ratio schedule in additional groups of (N=22) P rats. A moderate dose of topiramate (20mg/kg) was also included to verify topiramate's efficacy on its own.
Results: In P rats, but not in Wistar rats, the combination effectively and persistently reduced consumption; whereas, neither dose alone was effective. The combination and naltrexone alone were equally effective at reducing ethanol reinforcement; however, with the combination, but not naltrexone alone, this effect was selective for ethanol. All treatments produced a similar decrease in home-cage food consumption. The 20mg/kg dose of topiramate also effectively reduced ethanol consumption and reinforcement.
Conclusions: With greater efficacy and fewer side-effects, the combination shows promise as a treatment for AUDs.
(Copyright © 2013 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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