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)-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).
Gerasimov
M R
MR
Department of Chemistry, Brookhaven National Laboratory, Upton, NY 11973, USA.
Dewey
S L
SL
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D003932:Heroin / Q000494:pharmacology*; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020888:Vigabatrin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009294:Narcotics; D003932:Heroin; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D003042:Cocaine; D004298:Dopamine