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

Eur J Pharmacol. 1999 Sep 3;380(1):1-4. doi: 10.1016/s0014-2999(99)00526-9.

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).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-Aminobutyrate Transaminase / antagonists & inhibitors
  • Analysis of Variance
  • Animals
  • Cocaine / pharmacology*
  • Dopamine / metabolism*
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology*
  • Heroin / pharmacology*
  • Male
  • Narcotics / pharmacology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vigabatrin / pharmacology*

Substances

  • Enzyme Inhibitors
  • Narcotics
  • Heroin
  • 4-Aminobutyrate Transaminase
  • Vigabatrin
  • Cocaine
  • Dopamine