Chronic Kappa Oploid Receptor Antagonism Produces Supersensitivity to U-50,488H at the Hypothalamo-Pituitary-- Adrenocortical (H PA) Axis Level1

The present study was conducted to evaluate the influence of chronic kappa receptor blockade on the neuroendocrine effects of the selective kappa1 oploid agonist U-50,488H, on the hypo-thalamo-pituitary-adrenocortical (HPA) axis. Male Sprague-Daw-ley rats were chronically treated with naloxone (3 mg kg1 day1 for 7 days) or distilled water by s.c. implantation of osmotic minipumps and the response of the HPA axis to U-50,488H or saline was assessed before and 24 h after pump removal. Chronic infusion of naloxone reduced body weight gain and blocked the increase in corticosterone secretion induced by U-50,488H, indicating occupation of kappa opioid receptors. Sig-nificantly higher plasma corticosterone levels after U-50,488H administration at doses of 5 or 1 5 mg/kg were observed 1 day after cessation of naloxone treatment compared with those i