Biochemical and functional characterization of central dopamine receptors.

In order to characterize the D2 dopamine receptors at the molecular level we have developed procedures for purification and characterization of the receptor binding protein. The ligand binding sites of the D2 dopamine receptor have been identified by photoaffinity labeling with 3H-7-azidofluphenazine. The D2 dopamine receptor protein was partially purified by Fast Performance Liquid Chromatography on a Mono Q column and on a wheat-germ agglutinin agarose column. Some behavioral expressions which are probably mediated by D1 dopamine receptors were described. Evidence was obtained that catalepsy is associated with the blockade of D1 dopamine receptors and that D1 and D2 dopamine receptor systems interact either directly or indirectly in mediating this behavior. The administration of a dopamine agonist to monkeys with unilateral ventromedial tegmental lesions of the brainstem produced a biting behavior which, in some aspects, resembles the behavior in Lesch-Nyhan patients. The prevention of the dopamine agonist-induced biting behavior by the D1 dopamine antagonists indicates that D1 dopamine receptors are involved in the control of the expression of this behavior. The biting behavior, like other motor functions, might be controlled by the mesolimbic dopamine systems, and supersensitive mesolimbic D1 dopamine receptors might be associated with the pathology of this behavior.