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

Abstract

The cocaine congener [³H]CFT, also designated [³H]WIN 35,428 (2β;‐carbomethoxy‐3β;‐(4‐fluorophenyltropane)), labels cocaine receptors associated with the dopamine transporter in primate striatum. Autoradiogrpahic distribution of [³H]CFT binding (5 nM) in human postmortem control and Parkinson's‐diseased striatal tissue sections was compared. In control tissue, high and comparable levels of [³H]CFT binding were observed in the putamen and caudate nucleus. At least 90–99% of total [³H]CFT bound was inhibited by (—)‐cocaine (30 μM), suggesting that a high proportion of [³H]CFT is specifically bound. In Parkinson's‐diseased tissue, binding sites for [³H]CFT 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 [³H]CFT binding was observed, with the lateral caudate more severely depleted than the medial caudate. The marked decrease of [³H]CFT 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 [³H]CFT and the marked depletion of [³H]CFT‐labeled sites suggest that radiolabeled derivatives of CFT or its congeners may be suitable imaging probes for presynaptic dopamine nerve terminals.