Like many psychostimulant drugs,
nicotine elevates extracellular and synaptic
dopamine (DA) concentrations in the nucleus accumbens (NAc). This elevation has been linked to its reinforcing properties. Dopaminergic transmission within the NAc is modulated by
gamma-aminobutyric acid (
GABA). Therefore, we examined the utility of
gamma vinyl-GABA (GVG,
Vigabatrin) for inhibiting
nicotine's biochemical effects on NAc DA as well as its effects on behaviors associated with these biochemical changes. Given 2.5 hours prior to
nicotine, GVG (75 mg/kg) had no effect on
nicotine-induced increases in extracellular NAc DA. However, at 90 mg/kg, GVG significantly inhibited
nicotine-induced increases by approximately 50% while at 100 or 150 mg/kg, GVG completely abolished
nicotine-induced increases in both naive and chronically
nicotine-treated animals. When given 12 or 24 hours prior to
nicotine administration at a dose of 100 mg/kg, GVG-induced inhibition was diminished or abolished, respectively. In addition, at a dose of 18.75 mg/kg GVG abolished the expression of
nicotine-induced conditioned place preference (
CPP) while a dose of 75 mg/kg abolished the acquisition phase of
CPP. Finally, using positron emission tomography (PET) and 11C-raclopride in primates, GVG (100 mg/kg) abolished
nicotine-induced increases in synaptic DA while having no effect on the rate of metabolism of the radiotracer or its regional distribution. Together, these data suggest that GVG may be useful for the treatment of
nicotine addiction and further support the strategy of targeting the GABAergic system with a suicide inhibitor of
GABA-transaminase for the treatment of
drug addiction.