Author(s): Gerasimov MR, Dewey SL
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Abstract In the present study, we examined the effect of an acute administration of the selective suicide inhibitor of gamma-aminobutyric acid (GABA)-transaminase, gamma-vinyl GABA on increases in nucleus accumbens dopamine produced by a cocaine/heroin challenge in freely moving animals. Cocaine (20 mg/kg, i.p.) produced an elevation in extracellular nucleus accumbens dopamine of approximately 380\% above baseline, while heroin produced only a moderate increase of 70\%. Coadministration of these two drugs, however, produced a synergistic elevation in nucleus accumbens dopamine of 1000\%. This response was reduced by 50\% in animals pretreated with gamma-vinyl GABA (300 mg/kg, i.p.) 2.5 h prior to challenge. This same dose of gamma-vinyl GABA inhibited cocaine-induced increases in nucleus accumbens dopamine by 25\% and completely abolished heroin-induced increase. These findings indicate that gamma-vinyl GABA can interfere with the synergistic effects produced by the combination of an indirect dopamine releaser (heroin) and a dopamine reuptake blocker (cocaine).
This article was published in Eur J Pharmacol
and referenced in Journal of Addiction Research & Therapy