Catherine F Moore1, Omar A Protzuk1, Bankole A Johnson1, Wendy J Lynch2. 1. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States. 2. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, United States. Electronic address: wlynch@virginia.edu.
Abstract
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.
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.
Authors: Frank L Greenway; Ken Fujioka; Raymond A Plodkowski; Sunder Mudaliar; Maria Guttadauria; Janelle Erickson; Dennis D Kim; Eduardo Dunayevich Journal: Lancet Date: 2010-07-29 Impact factor: 79.321
Authors: Raymond F Anton; Stephanie S O'Malley; Domenic A Ciraulo; Ron A Cisler; David Couper; Dennis M Donovan; David R Gastfriend; James D Hosking; Bankole A Johnson; Joseph S LoCastro; Richard Longabaugh; Barbara J Mason; Margaret E Mattson; William R Miller; Helen M Pettinati; Carrie L Randall; Robert Swift; Roger D Weiss; Lauren D Williams; Allen Zweben Journal: JAMA Date: 2006-05-03 Impact factor: 56.272
Authors: Catherine F Moore; Matthew D Lycas; Colin W Bond; Bankole A Johnson; Wendy J Lynch Journal: Exp Clin Psychopharmacol Date: 2014-02 Impact factor: 3.157