Long-term changes in striatal D1 dopamine receptor distribution after dopaminergic deafferentation.
The morphochemical disposition of the adenylate cyclase-linked dopamine receptor (D1 type) in the rat striatum has been assessed at various time points after a neurotoxic lesion of the dopaminergic afferent pathway to the caudate nucleus. D1 receptor binding sites in the caudate nucleus were determined by in vitro autoradiography of the substituted benzazepine D1 antagonists, [3H]SCH 23390 or [125I]SCH 23982, and contrasted to the pattern of striatal immunohistochemical reactivity of the second messenger compound, cyclic 3',5'-adenosine monophosphate. The results demonstrate that the specific association of this dopamine receptor type with cyclic 3',5'-adenosine monophosphate-stained neurons is abolished at 7 days following chemical interruption of the nigrostriatal pathway, and the receptor disruption is persistent for durations as long as 20 weeks. This investigation suggests that once the postsynaptic receptor pathology is produced by deafferentation, it does not recover the selective morphochemical relationship normally established with the target cell containing the second messenger. This is in contrast to modest biochemical recuperation in D1 dopamine receptor binding seen using this experimental paradigm. This change in D1 dopamine receptor morphochemistry is discussed in relation to the neurochemical deficits produced by dopaminergic denervation and in Parkinson's disease.
Ariano
M A
MA
Department of Anatomy and Neurobiology, University of Vermont, College of Medicine, Burlington 05405.
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D001552:Benzazepines; D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D016627:Oxidopamine