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.
Stromberg
M F
MF
Center For Studies of Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. stromberg@research.trc.upenn.edu
Mackler
S A
SA
Volpicelli
J R
JR
O'Brien
C P
CP
Dewey
S L
SL
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