Effects of selective opioid-receptor blockade on the hypothalamo-pituitary-adrenocortical responses to surgical trauma in the rat

Abstract

ABSTRACT Opioid substances have been shown to stimulate and depress the secretion of ACTH in the rat. Their opposing actions appear to be mediated in part by specific receptors in the hypothalamus which influence the secretion of corticotrophin-releasing factor (CRF). In an attempt to determine the physiological role of these receptor systems, experiments were carried out in which the plasma ACTH and serum corticosterone concentrations were determined before and after stress in rats treated s.c. with selective antagonists of μ-(naloxone, naltrexone), δ-(ICI 174864) and κ-(MR2266) opioid receptors. Neither naloxone (25–100 μg/100 g) nor naltrexone (50 μg/100 g) influenced the resting plasma ACTH or serum corticosterone concentrations. However, both inhibited (P < 0·01) the secretion of the two hormones elicited normally by surgical stress (laparotomy under ether anaesthesia). ICI 174864 (30–100 μg/100 g) also had little effect on resting hypothalamo-pituitary-adrenocortical (HPA) activity but, at the highest dose, it caused a small (P < 0·05) potentiation of the response to surgery. In contrast, MR2266 (150–300 μg/100 g) produced marked activation of the HPA system and not only stimulated the resting secretion of ACTH and corticosterone but also potentiated and prolonged the HPA response to stress. The results suggest that μ- and κ-opioid receptors mediate opposing actions of endogenous opioid peptides, both of which may be physiologically important in the regulation of CRF release. Journal of Endocrinology (1989) 121, 213–220