The pathophysiological functions mediated by D1 dopamine receptors

The administration of the D1 DA receptor antagonist SCH 23390 produces catalepsy in rat, and this behavior can be abolished by pretreatment with selective D2 DA receptor agonists. The administration of mixed D1/D2 DA agonists, but not of selective D2 DA agonists, produces SMB behavior in monkeys with surgical unilateral VMT lesions of the brain stem. The DA agonist-induced SMB behavior is abolished by pretreatment of the monkeys with either the D1 DA antagonist SCH 23390 or with the mixed D1/D2 antagonist fluphenazine, but not with the selective D2 antagonist (+/-) sulpiride. A hypothetical relationship between abnormal guanine nucleotide metabolism in Lesch-Nyhan syndrome and the development of DA receptor supersensitivity is presented. The possible role of abnormal guanine nucleotide metabolism in some mental disorders associated with DA dysfunctions is discussed.