Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's‐diseased striatum

The cocaine congener 3HCFT, also designated 3HWIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluorophenyltropane), labels cocaine receptors associated with the dopamine transporter in primate striatum. Autoradiographic distribution of 3HCFT binding (5 nM) in human postmortem control and Parkinson's-diseased striatal tissue sections was compared. In control tissue, high and comparable levels of 3HCFT binding were observed in the putamen and caudate nucleus. At least 90-99% of total 3HCFT bound was inhibited by (-)-cocaine (30 microM), suggesting that a high proportion of 3HCFT is specifically bound. In Parkinson's-diseased tissue, binding sites for 3HCFT were reduced by 80% in the caudate nucleus and 96% in the putamen. This pattern of depletion parallels the previously reported loss of dopamine in these brain regions (Kish, Shannak, and Hornykiewicz, New Engl. J. Med., 318:876-880, 1988). In the dorsal caudate nucleus of Parkinson's-diseased tissue, a lateral-to-medial gradient of 3HCFT binding was observed, with the lateral caudate more severely depleted than the medial caudate. The marked decrease of 3HCFT binding sites in Parkinson's diseased striatum supports the following conclusions: 1) the dopamine transporter is localized primarily on presynaptic nigrostriatal terminals; 2) in the caudate and putamen, cocaine recognition sites are associated primarily with the dopamine transporter; 3) the low level of nonspecific binding of 3HCFT and the marked depletion of 3HCFT-labeled sites suggest that radiolabeled derivatives of CFT or its congeners may be suitable imaging probes for presynaptic dopamine nerve terminals.