Patricia Di Ciano1, Daniel F Manvich2, Abhiram Pushparaj1, Andrew Gappasov1, Ellen J Hess3, David Weinshenker2, Bernard Le Foll4,5,6,7,8,9,10. 1. Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto, M5S 2S1, Canada. 2. Department of Human Genetics, Emory University School of Medicine, Whitehead 301, 615 Michael St, Atlanta, GA, 30322, USA. 3. Department of Pharmacology and Neurology, Emory University, Atlanta, GA, USA. 4. Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto, M5S 2S1, Canada. Bernard.lefoll@camh.ca. 5. Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, Toronto, ON, Canada. Bernard.lefoll@camh.ca. 6. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. Bernard.lefoll@camh.ca. 7. Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada. Bernard.lefoll@camh.ca. 8. Department of Pharmacology, University of Toronto, Toronto, ON, Canada. Bernard.lefoll@camh.ca. 9. Department of Psychiatry, Division of Brain and Therapeutics, University of Toronto, Toronto, ON, Canada. Bernard.lefoll@camh.ca. 10. Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. Bernard.lefoll@camh.ca.
Abstract
RATIONALE: Gambling disorder is a growing societal concern, as recognized by its recent classification as an addictive disorder in the DSM-5. Case reports have shown that disulfiram reduces gambling-related behavior in humans. OBJECTIVES: The purpose of the present study was to determine whether disulfiram affects performance on a rat gambling task, a rodent version of the Iowa gambling task in humans, and whether any changes were associated with alterations in dopamine and/or norepinephrine levels. METHODS: Rats were administered disulfiram prior to testing on the rat gambling task or prior to analysis of dopamine or norepinephrine levels in brain homogenates. Rats in the behavioral task were divided into two subgroups (optimal vs suboptimal) based on their baseline levels of performance in the rat gambling task. Rats in the optimal group chose the advantageous strategy more, and rats in the suboptimal group (a parallel to problem gambling) chose the disadvantageous strategy more. Rats were not divided into optimal or suboptimal groups prior to neurochemical analysis. RESULTS: Disulfiram administered 2 h, but not 30 min, before the task dose-dependently improved choice behavior in the rats with an initial disadvantageous "gambling-like" strategy, while having no effect on the rats employing an advantageous strategy. The behavioral effects of disulfiram were associated with increased striatal dopamine and decreased striatal norepinephrine. CONCLUSIONS: These findings suggest that combined actions on dopamine and norepinephrine may be a useful treatment for gambling disorders.
RATIONALE: Gambling disorder is a growing societal concern, as recognized by its recent classification as an addictive disorder in the DSM-5. Case reports have shown that disulfiram reduces gambling-related behavior in humans. OBJECTIVES: The purpose of the present study was to determine whether disulfiram affects performance on a rat gambling task, a rodent version of the Iowa gambling task in humans, and whether any changes were associated with alterations in dopamine and/or norepinephrine levels. METHODS:Rats were administered disulfiram prior to testing on the rat gambling task or prior to analysis of dopamine or norepinephrine levels in brain homogenates. Rats in the behavioral task were divided into two subgroups (optimal vs suboptimal) based on their baseline levels of performance in the rat gambling task. Rats in the optimal group chose the advantageous strategy more, and rats in the suboptimal group (a parallel to problem gambling) chose the disadvantageous strategy more. Rats were not divided into optimal or suboptimal groups prior to neurochemical analysis. RESULTS:Disulfiram administered 2 h, but not 30 min, before the task dose-dependently improved choice behavior in the rats with an initial disadvantageous "gambling-like" strategy, while having no effect on the rats employing an advantageous strategy. The behavioral effects of disulfiram were associated with increased striatal dopamine and decreased striatal norepinephrine. CONCLUSIONS: These findings suggest that combined actions on dopamine and norepinephrine may be a useful treatment for gambling disorders.
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