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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on January 21, 2003; DOI: 10.1124/jpet.102.047712

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Vol. 305, Issue 1, 385-393, April 2003

Human Urocortin II, a Selective Agonist for the Type 2 Corticotropin-Releasing Factor Receptor, Decreases Feeding and Drinking in the Rat

Koki Inoue , Glenn R. Valdez, Teresa M. Reyes, Lindsay E. Reinhardt, Antoine Tabarin , Jean Rivier, Wylie W. Vale, Paul E. Sawchenko, George F. Koob and Eric P. Zorrilla

Department of Neuropharmacology (K.I., G.R.V., L.E.R., A.T., G.F.K., E.P.Z.), The Scripps Research Institute, La Jolla, California; Osaka City University Medical School (K.I.), Osaka, Japan; Neuronal Structure and Function (T.M.R., P.E.S.) and Peptide Biology Laboratory (J.R., W.W.V.), Salk Institute for Biological Studies, La Jolla, California; and University of Bordeaux (A.T.), Bordeaux, France

Corticotropin-releasing factor (CRF) has been hypothesized to modulate consummatory behavior through the Type 2 CRF (CRF2) receptor. However, behavioral functions subserved by the CRF2 receptor remain poorly understood. Recently, human urocortin II (hUcn II), a selective CRF2 receptor agonist, was identified. To study the effects of this neuropeptide on ingestive behavior, we examined the effects of centrally infused hUcn II (i.c.v. 0, 0.01, 0.1, 1.0, 10.0 µg) on the microstructure of nose-poke responding for food and water in nondeprived, male rats. Malaise-inducing properties of the peptide were monitored using conditioned taste aversion (CTA) testing. To identify potential sites of action, central induction of Fos protein expression was examined. hUcn II dose dependently reduced the quantity and duration of responding for food and water at doses lower (0.01-1.0 µg) than that forming a CTA (10 µg). Effects were most evident during hours 4 to 6 of the dark cycle. Meal pattern analysis showed that hUcn II potently (0.1 µg) increased the satiating value of food. Rats ate and drank smaller and shorter meals without changing meal frequency. Rats also ate more slowly. hUcn II induced Fos in regions involved in visceral sensory processing and autonomic/neuroendocrine regulation and resembling those activated by appetite suppressants. hUcn II is a promising neuropeptide for investigating the role of the CRF2 receptor in ingestive behavior.

0022-3565/03/3051-0385$07.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics


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