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  • Title: Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's-diseased striatum.
    Author: Kaufman MJ, Madras BK.
    Journal: Synapse; 1991 Sep; 9(1):43-9. PubMed ID: 1796351.
    Abstract:
    The cocaine congener [3H]CFT, also designated [3H]WIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluorophenyltropane), labels cocaine receptors associated with the dopamine transporter in primate striatum. Autoradiographic 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 microM), 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.
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