COCAINE USE INCREASES [H-3] WIN-35428 BINDING-SITES IN HUMAN STRIATUM

Animal studies suggest that chronic cocaine exposure may increase the function and/or synthesis of the dopamine transporter (DAT) under cert ain conditions, but the literature is complex. In order to test the hy pothesis that cocaine exposure alters the DAT in humans, preliminary s tudies were done characterizing [H-3]WIN 35428 binding in human striat um from normal controls. Following these experiments, the effects of c hronic cocaine were examined in post mortem striatal specimens from 7 cocaine users and 7 controls matched for age and post mortem interval, employing quantitative autoradiography. Initial saturation experiment s indicated that a one-site model was preferred with a K(d) of 11 +/- 4 nM. [H-3]WIN 35420 binding was then examined in cocaine users and co ntrols at 0.5, 5, 10, and 50 nM radioligand concentrations. At each co ncentration of [H-3]WIN 35420, optical densities for cocaine-exposed s ubjects were increased in caudate, putamen, and accumbens. The results suggest that total numbers of binding sites were increased in cocaine users. Based on the present and previous results, it appears that the regulation of the DAT is fairly plastic, and is highly sensitive to c ocaine dosing regimes and withdrawal intervals. Chronic adaptations in duced by cocaine in the DAT could contribute to the symptoms of bingin g, withdrawal depression, and/or craving.