Gamma-vinyl gamma-aminobutyric acid attenuates the synergistic elevations of nucleus accumbens dopamine produced by a cocaine/heroin (speedball) challenge

In the present study, we examined the effect of an acute administration of the selective suicide inhibitor of gamma-aminobutyric acid (GABA)-transamin ase, gamma-vinyl GABA on increases in nucleus accumbens dopamine produced b y a cocaine/heroin challenge in freely moving animals. Cocaine (20 mg/kg, i .p.) produced an elevation in extracellular nucleus accumbens dopamine of a pproximately 380% above baseline, while heroin produced only a moderate inc rease of 70%. Coadministration of these two drugs, however, produced a syne rgistic 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 c ocaine-induced increases in nucleus accumbens dopamine by 25% and completel y abolished heroin-induced increase. These findings indicate that gamma-vin yl GABA can interfere with the synergistic effects produced by the combinat ion of an indirect dopamine releaser (heroin) and a dopamine reuptake block er (cocaine). (C) 1999 Elsevier Science B.V. All rights reserved.