Possible mechanism of hypothermia induced by intracerebroventricular injection of orphanin FQ/nociceptin

Orphanin/nociceptin (OFQ/N), a 17-amino-acid peptide, is an endogenous peptide, the receptor for which is similar to mu-, delta- and kappa -opioid receptors (similar to 65% homology). Reports indicate that OFQ/N can block the antinociception induced by mu-, delta- and kappa -opioid agonists in the rat and in the mouse, indicating that then is a functional interaction between opioid receptors and OFQ/N receptors in the nervous system. It is well known that activation of the mu- and kappa -opioid receptors results in hyperthermia and hypothermia, respectively, in Sprague-Dawley rats. The present studies were designed to examine effects of OFQ/N on body temperature (T-b) and explore whether the mechanism of T-b change induced by OFQ/N involved the opioid system. The results show that (1) i.c.v. injection of a high dose of OFQ/N (9-18 mug) produces hypothermia in adult rats: (2) OFQ/N (1.8 mug, i.c.v., t=+30 s after morphine) can decrease morphine-induced hyperthermia; (3) neither the opioid receptor antagonist, naloxone (10 mg/kg, s.c., t= -15 s before OFQ/N) nor the kappa -opioid receptor antagonist nor-BNI (1 mug/5 mul, i.c.v., t= -30 s before OFQ/N) reduces the hypothermia induced by i.c.u. injection of OFQ/N at dose of 18 mug (P >0.05); (4) 60 mug/5 mul AS oligo (i.c.v. treatment on days 1, 3 and 5) against OFQ/N receptors significantly reduces the hypothermia induced by i.c.v. injection of 9 mug OFQ/N (P <0.01). These results suggest that the hypothermia induced by i.c.v. injection of a high dose of OFQ/N (9 or 18 mug) is mediated, at least partially, by its own receptor, independent or downstream of opioid receptors in the rat brain and that OFQ/N probably acts as a physiological antagonist to reduce morphine-induced hyperthermia. (C) 2001 Elsevier Science B.V. All rights reserved.