Effects of acute and chronic administration of mu- and delta-opioid agonists on the hypothalamic-pituitary-adrenocortical (HPA) axis in the rat.

The control of hypothalamic-pituitary-adrenocortical (HPA) activity by opioids seems to involve stimulatory and inhibitory pathways. The purpose of the present study was to determine the acute and chronic effects of selective mu- and delta-opioid agonists, administered centrally (i.c.v.) on pituitary-adrenocortical activity in the rat. The mu-agonist DAGO ([D-Ala2,N-MePhe4,Gly-ol5]enkephalin; 0.75 nmol i.c.v.) and the delta-agonist DPDPE ([D-Pen2,5]enkephalin; 194 nmol i.c.v.) both stimulated corticosterone release when administered acutely. Chronic administration of DAGO and DPDPE resulted in the development of tolerance to their neuroendocrine effects. These data suggest that both mu- and delta-opioid receptors are involved in the regulation of HPA activity under physiological conditions and during opiate abuse.