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Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's‐diseased striatum
Author(s) -
Kaufman Marc J.,
Madras Bertha K.
Publication year - 1991
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890090107
Subject(s) - putamen , caudate nucleus , dopamine transporter , striatum , dopamine , dopamine plasma membrane transport proteins , chemistry , basal ganglia , medicine , neuroscience , endocrinology , biology , central nervous system , dopaminergic
The cocaine congener [ 3 H]CFT, also designated [ 3 H]WIN 35,428 (2β;‐carbomethoxy‐3β;‐(4‐fluorophenyltropane)), labels cocaine receptors associated with the dopamine transporter in primate striatum. Autoradiogrpahic distribution of [ 3 H]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 [ 3 H]CFT binding were observed in the putamen and caudate nucleus. At least 90–99% of total [ 3 H]CFT bound was inhibited by (—)‐cocaine (30 μM), suggesting that a high proportion of [ 3 H]CFT is specifically bound. In Parkinson's‐diseased tissue, binding sites for [ 3 H]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 [ 3 H]CFT binding was observed, with the lateral caudate more severely depleted than the medial caudate. The marked decrease of [ 3 H]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 [ 3 H]CFT and the marked depletion of [ 3 H]CFT‐labeled sites suggest that radiolabeled derivatives of CFT or its congeners may be suitable imaging probes for presynaptic dopamine nerve terminals.