THE experiments presented in this study were designed to assess corticotropin-releasing factor (CRF) receptor subtype mediation of CRF-and urocortin (UCN)-induced decrease in food intake. Male Sprague—Dawley rats were treated with antisense and sense oligo-nucleotides (ON) to CRF2receptor mRNAs for 3 6 h and then received an intracerebroventricular (i.c.v.) injection of CRF, UCN β3 μg) or saline. Antisense treatment significantly attenuated CRF-and UCN-induced suppression in food intake and HPA activation. Administration of CRF1receptor antagonist did not affect the decrease in food intake or activation of the HPA axis induced by ICV infusion of 3μg CRF. The data suggest that down-regulation of CRF2receptors selectively attenuates CRF-and UCN-induced anorexia and hypothalamo-pituitary-adrenocortical activation in rats.