INVIVO VOLTAMMETRIC STUDIES ON RELEASE MECHANISMS FOR COCAINE WITH GAMMA-BUTYROLACTONE

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, gamma-butyrolactone (gamma-BL). The results were compared with cocaine effects on accumbens DA and 5-HT in the freely moving rat, without gamma-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 gamma-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 gamma-BL (50.6%). The findings show that cocaine's effects on synaptic concentrations for DA and for 5-HT in accumbens are dependent on neuronal impulse flow. The findings indicate that presynaptic releasing mechanisms, which may be different for DA vis-a-vis 5-HT, play a role in the mechanism of action of cocaine.