In vivo 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 less than 0.0001) after DA impulse flow was significantly inhibited (p less than 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 less than 0.0004) after impulse flow was significantly inhibited (p less than 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-à-vis 5-HT, play a role in the mechanism of action of cocaine.
Broderick
P A
PA
Department of Pharmacology, City University of New York Medical School, NY.
D015107:4-Butyrolactone / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012054:Reinforcement, Psychology; D012701:Serotonin / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D012701:Serotonin; D003042:Cocaine; D015107:4-Butyrolactone; D004298:Dopamine