QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.068676v1 310/3/1027    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zorrilla, E. P. Articles by Koob, G. F. Search for Related Content PubMed PubMed Citation Articles by Zorrilla, E. P. Articles by Koob, G. F.

BEHAVIORAL PHARMACOLOGY

Human Urocortin 2, a Corticotropin-Releasing Factor (CRF)₂ Agonist, and Ovine CRF, a CRF₁ Agonist, Differentially Alter Feeding and Motor Activity

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California (E.P.Z., L.E.R., G.R.V., K.I., G.F.K.); Department of Neuropsychiatry, Osaka City University Medical School, Osaka, Japan (K.I.); and Peptide Biology Laboratory, The Salk Institute for Biological Sciences, La Jolla, California (J.E.R., W.W.V.)

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 µg), 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 µg) 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.

Address correspondence to: Dr. Eric P. Zorrilla, Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. E-mail: ezorrilla{at}scripps.edu

This article has been cited by other articles:

				T. Nemoto, N. Yamauchi, and T. Shibasaki Novel action of pituitary urocortin 2 in the regulation of expression and secretion of gonadotropins J. Endocrinol., April 1, 2009; 201(1): 105 - 114. [Abstract] [Full Text] [PDF]

				Y. Zhao, G. R. Valdez, E. M. Fekete, J. E. Rivier, W. W. Vale, K. C. Rice, F. Weiss, and E. P. Zorrilla Subtype-Selective Corticotropin-Releasing Factor Receptor Agonists Exert Contrasting, but Not Opposite, Effects on Anxiety-Related Behavior in Rats J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 846 - 854. [Abstract] [Full Text] [PDF]

				V. P. Bakshi, S. M. Newman, S. Smith-Roe, K. A. Jochman, and N. H. Kalin Stimulation of Lateral Septum CRF2 Receptors Promotes Anorexia and Stress-Like Behaviors: Functional Homology to CRF1 Receptors in Basolateral Amygdala J. Neurosci., September 26, 2007; 27(39): 10568 - 10577. [Abstract] [Full Text] [PDF]

				P. Cottone, V. Sabino, T. R. Nagy, D. V. Coscina, and E. P. Zorrilla Feeding microstructure in diet-induced obesity susceptible versus resistant rats: central effects of urocortin 2 J. Physiol., September 1, 2007; 583(2): 487 - 504. [Abstract] [Full Text] [PDF]

				A. Legendre, E. Papakonstantinou, M.-C. Roy, D. Richard, and R. B. S. Harris Differences in response to corticotropin-releasing factor after short- and long-term consumption of a high-fat diet Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1076 - R1085. [Abstract] [Full Text] [PDF]

				B. Henry, W. Vale, and A. Markou The Effect of Lateral Septum Corticotropin-Releasing Factor Receptor 2 Activation on Anxiety Is Modulated by Stress J. Neurosci., September 6, 2006; 26(36): 9142 - 9152. [Abstract] [Full Text] [PDF]