Cocaine: On-line analysis of an accumbens amine neural basis for psychomotor behavior

Dose-response studies on subcutaneous cocaine were done to ascertain its effects in nucleus accumbens in dopaminergic and serotonergic neuronal circuitry in the behaving rat with in vivo voltammetry. Simultaneously, and at each dose of cocaine, unconditioned psychomotor stimulant behavior induced by cocaine was studied in terms of multiple concurrent measures of spontaneous behavior and by activity patterns of locomotion. Time course studies showed that the neurochemical effects of cocaine (10, 20, and 40 mg/kg SC) significantly (p<0.001) increased accumbens synaptic concentrations of dopamine (DA) and concurrently and significantly (p<0.0001) decreased accumbens synaptic concentrations of serotonin (5-HT) in a dose response manner. Simulataneous behavioral time course studies showed that cocaine (10, 20, and 40 mg/kg SC) significantly (p<0.0001) increased ambulations (locomotor activity), fine movements (stereotypic movements of sniffing and grooming) and rearing behavior, while significantly decreasing agoraphobic behavior, as measured by a statistically significant increase in central ambulations (p<0.0001). The high dose of cocaine (40 mg/kg SC) significantly increased fine movements over those produced by the lower doses of cocaine (p<0.0002). One import of the findings is that the DA and 5-HT biogenic amine response occurs in a behavioral paradigm of psychomotor stimulation, which is a known measure of reinforcement. Another is that the biogenic amines DA and 5-HT are affected by cocaine in this reinforcement paradigm with exactly opposite directionality. Finally, acute cocaine administration is shown to produce a dose response inhibition of agoraphobia (fear),w hich is highly correlated (ϱ=.983, p<0.01) with the opposing effects of cocaine on the accumbens biogenic amines, DA and 5-HT.