Dopamine receptor changes following destruction of the nigrostriatal pathway: lack of a relationship to rotational behavior.
Phenomena consistent with postsynaptic supersensitivity developed in the rat neostriatum following the destruction of dopaminergic afferent neurons. A gradual increase in the density of binding sites for [3H]spiperone occurred over a 2-3 week period. This increase was apparent only after the almost complete loss of dopamine-containing nerve terminals as measured by the depletion of endogenous dopamine. The properties of the receptor labeled by [3H]spiperone were not altered by denervation. Elimination of dopamine-containing nerve endings in the neostriatum was accompanied by the gradual development of an increase in dopamine-sensitive adenylate cyclase activity in homogenates of the caudate ipsilateral to the lesion as compared to the contralateral side. The administration of apomorphine led to pronounced circling behavior. This effect occurred rapidly and was maximal within 3 days following destruction of dopaminergic neurons. The increase in the density of dopamine receptors and in a receptor-mediated function may partially account for the development of enhanced electrophysiological responses to dopamine agonists in the neostriatum. However, the results do not explain the drug-induced rotational behavior which develops after destruction of the dopamine-containing nigrostriatal pathway. This behavioral phenomenon clearly preceded the appearance of receptor alterations in the corpus striatum.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009068:Movement / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D013134:Spiperone; D000262:Adenylyl Cyclases; D001058:Apomorphine; D004298:Dopamine