EVIDENCE FOR CENTRAL AND PERIPHERAL SEROTONERGIC CONTROL OF CORTICOSTERONE SECRETION IN THE CONSCIOUS RAT

Serotonin (5-HT) and 5-HTagonists act on multiple 5-HT receptor subtypes to increase corticosterone secretion. The present experiments describe the effects of a highly selective 5-HT2 receptor agonist DOI [(±)-1 -(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1] on plasma corticosterone in conscious, unrestrained, male rats with indwelling arterial and venous catheters. DOI (500 µg/kg, i.v.) increased plasma corticosterone levels 6- to 7-fold from 15 to 60 min. Pretreatment with the central 5-HT2 antagonist LY 53857 (100 µg/kg, i.v.) blocked the effect of DOI on corticosterone secretion at all times. The peripheral 5-HT2 antagonist xylamidine (100 µg/kg, i.v.) attenuated the corticosterone response elicited 15 min after DOI but did not alter the 60-min response. In contrast, dexamethasone pretreatment (350 µg/kg, s.c) attenuated the corticosterone response to DOI at 15 min, but abolished the response at 60 min. The increase in corticosterone levels elicited 5 min after the nonselective 5-HT agonist quipazine (3 mg/kg, i.v.) was also reduced by xylamidine. These data suggest that 5-HT: receptor agonists increase corticosterone secretion initially, in part, through a direct adrenal mechanism not entirely dependent on adrenocorticotropin, and at later times via a central, dexamethasone-suppressibie mechanism. This raises the possibility that endogenous 5-HT in the adrenal medulla may act as a local paracrine to participate in the regulation of corticosterone secretion from the adrenal cortex. © 1990 S. Karger AG, Basel.