Abstract

Genetic manipulations of corticotropin-releasing factor (CRF)₁ and CRF₂ receptors have resulted in data suggesting that the CRF₂ receptor could mediate 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,L18,21E30, A32,K33]sucker fish urotensin (12-41)NH₂ [cUTSN (12-41)] with a small-molecule CRF₁-selective antagonist, NBI-27914, and a CRF₂-selective peptide antagonist, antisauvagine-30, to attenuate the anorexic effects of CRF. We also monitored other behaviors that accompanied CRF-induced anorexia. CRF-induced anorexia was significantly correlated with a reduction in locomotor activity and an increase in freezing behavior and piloerection. cUTSN (12-41) and antisauvagine-30 significantly attenuated the effects of CRF (0.04 nmol) on 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 nmol/2.5 μl or when given orally at 20 to 40 mg/kg. Although these data support the hypothesis that the CRF₂ receptor mediates the appetite suppression induced by CRF, they also suggest that the CRF₂ receptor could mediate the stress-like behaviors that accompany CRF-induced appetite suppression.