Gamma-vinyl GABA inhibits methamphetamine, heroin, or ethanol-induced increases in nucleus accumbens dopamine

We examined the acute effect of the irreversible GABA-transaminase inhibito r, gamma-vinyl GABA (GVG, Sabril(R), Vigabatrin(R)) on increases in nucleus accumbens (NAc) dopamine (DA) folio-wing acute administration of methamphe tamine, heroin, or ethanol. Methamphetamine (2.5 mg/kg) produced a dose-dep endent increase (2,700%) in NAc DA. GVG preadministration (300 or 600 mg/kg ), however, inhibited this response by approximately 39 and 61%, respective ly. The lower dose of methamphetamine (1.25 mg/kg), increased DA by 1,700%. This response was inhibited to a similar extent (44%) regardless of the GV G dose preadministered (300 or 600 mg/kg). in addition, heroin-induced incr eases in NAc DA (0.5 mg/kg, 170%) were inhibited or completely abolished by GVG (150 or 300 mg/kg, 65 and 100%, respectively). Finally, at half the do se necessary for heroin, GVG (150 mg/kg) also completely abolished ethanol- induced increases in NAc DA following a 0.25 g/kg challenge dose (140%). Ta ken with our previous findings using nicotine or cocaine as the challenge d rug, these results indicate that GVG attenuates increases in NAc DA by a me chanism common to many drugs of abuse. However, it appears unlikely that an acute dose of GVG can completely inhibit increases in NAc DA following cha llenges with a drug whose mechanism of action is mediated primarily through the DA reuptake site. (C) 1999 Wiley-Liss, Inc.