title: Human urocortin 2, a corticotropin-releasing factor (CRF)2 agonist, and ovine CRF, a CRF1 agonist, differentially alter feeding and motor activity.
abstract: Two corticotropin-releasing factor (CRF) receptor families have been identified (CRF1 and CRF2). Whereas anxiogenic-like roles for the CRF1 receptor have been identified, behavioral functions of the CRF2 receptor remain obscure. Urocortin 2 (Ucn 2), a CRF-related peptide that selectively binds CRF2 receptors, was recently identified and recognized for its central anorectic properties. The present study tested the hypothesis that the anorexigenic mode of action of Ucn 2 differed from that of ovine CRF (oCRF), a preferential CRF1 receptor agonist. The behavioral effects of intracerebroventricular administration of Ucn 2 were compared with those of oCRF in nondeprived male Wistar rats (n=102). Ucn 2 reduced 6-h food and water intake at doses that did not induce visceral illness (0.1, 1, and 10 microg), as indicated by kaolin intake. Ucn 2 retained its potent anorectic activity in rats receiving a highly palatable cafeteria diet, preferentially reducing intake of carbohydrate (CHO)-rich items while sparing intake of mixed-fat/CHO items. In contrast to Ucn 2, oCRF (10 microg) suppressed 6-h intake of cafeteria diet-fed rats without regard to macronutrient composition. Rather, oCRF most potently suppressed intake of preferred food items. Whereas oCRF had short-onset motor-activating effects, Ucn 2 had nondose-dependent, delayed-onset motor-suppressing effects. Thus, central infusion of a CRF2 receptor agonist suppressed intake of both bland and palatable diets without inducing behavioral arousal or malaise, and the profile of anorexigenic effects qualitatively differed from those of a CRF1 receptor agonist. The results suggest the existence of distinct forms of CRF1- and CRF2-mediated anorexia.
authors.affiliation: Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ezorrilla@scripps.edu
authors.forename: Eric P
authors.initials: EP
authors.lastname: Zorrilla
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Reinhardt
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Valdez
authors.forename: Koki
authors.initials: K
authors.lastname: Inoue
authors.forename: Jean E
authors.initials: JE
authors.lastname: Rivier
authors.forename: Wylie W
authors.initials: WW
authors.lastname: Vale
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects* / Q000502:physiology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007616:Kaolin; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism*; D012756:Sheep; D054832:Urocortins; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D007616:Kaolin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone