The effect of gamma-vinyl-GABA on the consumption of concurrently available oral cocaine and ethanol in the rat.
It has frequently been reported that a high percentage of individuals, identified as either alcohol- or cocaine-dependent, concurrently abuse both drugs. The experiments reported here represent a continuing effort to develop an animal model to predict the effects of a potential pharmacotherapeutic agent on concurrently available oral ethanol and cocaine. These experiments utilized drinkometer circuitry to assess the effects of gamma-vinyl-GABA (GVG), a gamma-aminobutyric acid (GABA) transaminase inhibitor, on the consumption and temporal pattern of responses for orally self-administered ethanol and cocaine. The results of these experiments showed that GVG, at doses of 100, 200 and 300 mg/kg, reduced both ethanol and cocaine consumption in a dose-related manner. When compared to vehicle, GVG at all doses significantly reduced ethanol consumption while consumption of cocaine was significantly reduced only at 300 mg/kg. This is consistent with data showing that GVG reduces consumption of these drugs when administered alone and data showing that GVG is more potent in reducing ethanol-induced compared to cocaine-induced extracellular dopamine in the nucleus accumbens. Analysis of the temporal pattern of drinking across the session suggests that GVG's effects are due to a disruption of the reinforcing properties of ethanol and cocaine rather than a more general reduction in motor behavior. These data suggest that GVG has potential for clinical use in populations that abuse either alcohol or cocaine alone or in combination.
Center For Studies of Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. stromberg@research.trc.upenn.edu
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Stromberg
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Mackler
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Volpicelli
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O'Brien
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Dewey
D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy; D003042:Cocaine / Q000031:analogs & derivatives* / Q000097:blood; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D020888:Vigabatrin / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; C005618:benzoylecgonine; D020888:Vigabatrin; D003042:Cocaine