Citation

Gerasimov MR, Dewey SL. Eur. J. Pharmacol. 1999; 380(1): 1-4.

Copyright

(Copyright © 1999, Elsevier Publishing)

DOI

10.1016/s0014-2999(99)00526-9

PMID

10513553

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).

Language: en

Keywords

4-Aminobutyrate Transaminase; Analysis of Variance; Animals; Cocaine; Dopamine; Drug Synergism; Enzyme Inhibitors; Heroin; Male; Narcotics; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Time Factors; Vigabatrin