Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease.
Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3H-spiperone (3H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3H-SP in dopamine-denervated compared with intact striata. 3H-SP in vivo binds to less than 10% of striatal sites labeled by 3H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3H-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 3H-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.
Bennett
J P
JP
Wooten
G F
GF
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D005374:Filtration / Q000379:methods; D007700:Kinetics; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium
D002090:Butyrophenones; D011954:Receptors, Dopamine; D014316:Tritium; D013134:Spiperone; D004298:Dopamine