DIFFERENT EFFECTS OF COCAINE AND NOMIFENSINE ON DOPAMINE UPTAKE IN THE CAUDATE-PUTAMEN AND NUCLEUS-ACCUMBENS

The effects of cocaine and nomifensine on the uptake of dopamine have been compared in the caudate-putamen and nucleus accumbens of rat brai n slices. Electrical stimulation of brain slices was used to evoke dop amine efflux and the changes in dopamine concentration in the extracel lular fluid were monitored with fast-scan cyclic voltammetry with Nafi oncoated, carbon-fiber electrodes. The disappearance of extracellular dopamine after the stimulation fit Michaelis-Menten kinetics in both r egions. Cocaine and nomifensine were found to competitively inhibit do pamine uptake in both regions. The competitive mechanism of action was apparent in the primary data because the initial uptake rates were un changed by low doses of inhibitor, but dopamine uptake was slowed at c oncentrations near the K-m value. In both regions, the apparent K-m va lue increased with higher concentrations of cocaine (0.01-60 mu M) or nomifensine (0.01-30 mu M) in the perfusion buffer. The apparent K-m v alues were used to obtain inhibition constants (K-i values) for the up take inhibitors in each region. This analysis showed that cocaine had a K-i of 0.29 mu M in both regions. Nomifensine, however, had a signif icantly higher potency in the caudate-putamen (K-i = 0.09 mu M) than i n the nucleus accumbens (K-i = 0.21 mu M). These results show that the re are differential effects of uptake inhibitors in different brain re gions, and suggest that the dopamine transporter exhibits cell-specifi c regulation.