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 ( approximately 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 there 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 (Tb) 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 micro g) produces hypothermia in adult rats; (2) OFQ/N (1.8 micro g, 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 micro g/5 microl, i.c.v., t=-30 s before OFQ/N) reduces the hypothermia induced by i.c.v. injection of OFQ/N at dose of 18 micro g (P>0.05); (4) 60 micro g/5 microl 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 micro g 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 micro g) 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.
Chen
X
X
Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA. chenyang@astro.ocis.temple.edu
McClatchy
D B
DB
Geller
E B
EB
Liu-Chen
L
L
Tallarida
R J
RJ
Adler
M W
MW
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D007035:Hypothermia / Q000139:chemically induced*; D007276:Injections, Intraventricular; D008297:Male; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D000097629:Nociceptin
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000097629:Nociceptin