In vivo voltammetric studies on release mechanisms for cocaine with γ-butyrolactone

Broderick, Patricia A.

The effect of cocaine (20 mg/kg SC) on presynaptic mechanisms of release for dopamine (DA) and for serotonin (5-HT) was studied in nucleus accumbens of unrestrained rats (Rattus norvegicus). The studies were done by assaying synaptic concentrations of DA and 5-HT in the presence of the neuronal impulse flow inhibitor, γ-butyrolactone (γ-BL). The results were compared with cocaine effects on accumbens DA and 5-HT in the freely moving rat, without γ-BL treatment. A neurochemical time course profile showed that the cocaine-induced increase in accumbens synaptic concentrations of DA was significantly blocked (p<0.0001) after DA impulse flow was significantly inhibited (p<0.0038) by γ-BL (35.8%). The neurochemical time course profile concurrently showed that the cocaine-induced decrease in accumbens synaptic concentrations of 5-HT was significantly blocked (p<0.0004) after impulse flow was significantly inhibited (p<0.025) by γ-BL (50.6%). The findings show that cocaine's effects on synaptic concentrations for DA and for HT in accumbens are dependent on neuronal impulse flow. The findings indicate that presynaptic releasing mechanisms, which may be different for DA vis-à -vis 5-HT, play a role in the mechanism of action of cocaine.