title: Orphanin FQ-induced hyperphagia is mediated by corticosterone and central glucocorticoid receptors.
abstract: Orphanin FQ (Nociceptin) has been reported to stimulate food intake in satiated rats and to stimulate corticosterone release. A large body of evidence exists to link central feeding systems with the regulation of corticosterone. In this study, we sought to determine whether or not circulating corticosterone is necessary for the induction of food intake by Orphanin FQ. We found that intracerebroventricular injection of Orphanin FQ (0.64-5 nmoles) dose dependently stimulated food intake and plasma corticosterone within 30 min of injection. Removal of corticosterone, by adrenalectomy, abolished the hyperphagic effect of Orphanin FQ. The stimulatory effect of Orphanin FQ on food intake was still negated following a low dose of corticosterone replacement (corresponding to a plasma corticosterone concentration of 1.86+/-0.99 microg/dl). However, following a larger dose of corticosterone replacement (corresponding to a plasma corticosterone concentration of 8.92+/-0.55 microg/dl) the feeding effect was fully restored. We concluded this study by testing the glucocorticoid receptor antagonist, RU486 (Mifepristone, 80 microg/2 microl) on Orphanin FQ-induced feeding. Central injection of RU486, 30 min prior to injection of Orphanin FQ, significantly reduced Orphanin FQ-induced food intake in comparison to vehicle-treated controls. Overall, these data demonstrate the necessity for circulating corticosterone in the mediation of Orphanin-FQ-induced feeding and suggest that the mechanism through which the hyperphagic effect is obtained involves activation of central glucocorticoid receptors.
authors.affiliation: Mental Health Research Institute, University of Michigan School of Medicine, 205 Zina Pitcher Place, Ann Arbor 48109-0720, USA. janetnic@umich.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Nicholson
authors.forename: H
authors.initials: H
authors.lastname: Akil
authors.forename: S J
authors.initials: SJ
authors.lastname: Watson
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D006963:Hyperphagia / Q000139:chemically induced / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*; D000097629:Nociceptin
chemical_list: D003345:Corticosterone; D006727:Hormone Antagonists; D015735:Mifepristone; D018847:Opioid Peptides; D011965:Receptors, Glucocorticoid; D014665:Vasodilator Agents; D000097629:Nociceptin