GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine

Environments previously associated with drug use can become one of the most common factors triggering relapse to drug-seeking behavior. To better unde rstand the neurochemical mechanisms potentially mediating these cues, we me asured nucleus accumbens dopamine levels in animals exposed to environmenta l cues previously paired with cocaine administration. In animals exposed to a cocaine-paired environment nucleus accumbens dopamine increased by 25%. When administered 2.5 h prior to presentation of the environmental trigger, racemic vigabatrin tan irreversible inhibitor of gamma -aminobutyric acid (GABA)-transaminase) abolished this cue-induced increase. Conversely, R-(-) -vigabatrin, the inactive enantiomer, had no effect. Combined with our earl ier findings, these studies support the potential therapeutic benefit of th is enzyme-based GABAergic strategy to modulate brain dopamine and the subse quent treatment of drug addiction. (C) 2001 Elsevier Science B.V. All right s: reserved.