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Dopamine denervation does not alter in vivo 3 H‐spiperone binding in rat striatum: Implications for external imaging of dopamine receptors in Parkinson's disease
Author(s) -
Bennett James P.,
Wooten G. Frederick
Publication year - 1986
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410190412
Subject(s) - dopamine , striatum , dopaminergic , in vivo , substantia nigra , chemistry , denervation , medicine , endocrinology , dopamine receptor , biology , microbiology and biotechnology
Striatal particulate preparations, both from rats with lesion‐induced striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H‐neuroleptic binding, which is interpreted to be the mechanism of denervation‐induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H‐spiperone ( 3 H‐SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate‐bound 3 H‐SP in dopamine‐denervated compared with intact striata. 3 H‐SP in vivo binds to less than 10% of striatal sites labeled by 3 H‐SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H‐SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H‐SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H‐SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo–administered 3 H‐SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo.