Role of Corticotropin-Releasing Factor (CRF) Receptors in the Anorexic Syndrome Induced by CRF

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 CRFon appetiteor satiety. We have attempted to obtain pharmacological evidence for this hypothesis by comparing the ability of a high-affinity peptide, mixed CRFantagonist [cyclo 30-33,f12,L18,21E30, A32,K33] suckerfish urotensin(12-41)NH 2 [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 anorexiawas significantly correlated with a reduction in locomotor activity and an increase in freezing behaviorand piloerection. cUTSN (12-41) and antisauvagine-30 significantly attenuated the effects of CRF(0.04 nmol) on food intake along with the behavioral syndromethat 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 appetitesuppression induced by CRF, they also suggest that the CRF2 receptor could mediate the stress-like behaviors that accompany CRF-induced appetitesuppression.