Role of corticotropin-releasing factor (CRF) receptors in the anorexic syndrome induced by CRF

Genetic manipulations of corticotropin-releasing factor (CRF)(1) and CRF2 r eceptors have resulted in data suggesting that the CRF2 receptor could medi ate the effects of CRF on appetite or satiety. We have attempted to obtain pharmacological evidence for this hypothesis by comparing the ability of a high-affinity peptide, mixed CRF antagonist [cyclo 30-33,f12,L18,21 E30, A3 2,K33]sucker fish urotensin (12-41)NH2 [cUTSN (12-41)] with a small-molecul e CRF1-selective antagonist, NBI-27914, and a CRF2-selective peptide antago nist, antisauvagine-30, to attenuate the anorexic effects of CRF. We also m onitored other behaviors that accompanied CRF-induced anorexia. CRF-induced anorexia was significantly correlated with a reduction in locomotor activi ty and an increase in freezing behavior and piloerection. cUTSN (12-41) and antisauvagine-30 significantly attenuated the effects of CRF (0.04 nmol) o n food intake along with the behavioral syndrome that accompanied anorexia. In contrast, NBI-27914 did not attenuate either of the above-mentioned CRF -induced phenomena when given centrally at doses ranging from 0.13 to 10 nm o1/2.5 mu l or when given orally at 20 to 40 mg/kg. Although these data sup port the hypothesis that the CRF2 receptor mediates the appetite suppressio n induced by CRF, they also suggest that the CRF2 receptor could mediate th e stress-like behaviors that accompany CRF-induced appetite suppression.