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 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.