A stimulatory role for endogenous dopamine (DA) in the regulation of hypothalamo-pituitary-adrenal activity has previously been demonstrated. In the present study, the roles of D1 and D2 subtypes of DA receptors in the regulation of activity of the hypothalamo-pituitary-adrenal axis were investigated. The intraperitoneal administration of either the D1 agonist, SKF 383393 (1-phenyl-2,3,4,5 tetrahydro-(iH)-benzazepine-7,8diol HCl, 5-20 mg/kg) or the D2 agonist quinpirole (0.05-1 mg/kg) dose-dependently elevated both adrenocorticotropic hormone (ACTH) and corticosterone (CS) in serum. Similarly, administration of either SKF 38393 or quinpirole (1-100 micrograms) into the third ventricle dose-dependently elevated ACTH in serum. The response of ACTH to intraperitoneal SKF 38393 was blocked by pretreatment with the D1 antagonist SCH 23390 (1-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5 tetrahydro-1H-3-benzazepine, 0.25 mg/kg, i.p.) but not by the D2 antagonist sulpiride (50 mg/kg, i.p.). The response of ACTH to intraperitoneal injection of quinpirole was blocked by pretreatment with sulpiride and attenuated slightly by pretreatment with SCH 23390. Further, the co-administration of sub-maximum doses of SKF 38393 and quinpirole caused additive increases in ACTH in serum. These results suggest that both D1 and D2 subtypes of DA receptors contribute to the dopaminergic regulation of function of the hypothalamo-pituitary-adrenal axis and support a role for DA neurons in the hypothalamus in this response. Further, these findings suggest that the D1 and D2 receptors, mediating the response of the hypothalamopituitary-adrenal axis are not tightly coupled.(ABSTRACT TRUNCATED AT 250 WORDS)