Influence of peptide CRF receptor antagonists upon the behavioural effects of human/rat CRF.

The effects of the corticotropin-releasing factor (CRF) receptor antagonists, alpha-helical CRF-(9-41), [D-Phe12,Nle21,38, CalphaMe-Leu37]humanCRF-(12-41) (D-PheCRF-(12-41)) and astressin ([cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]h umanCRF-(12-41) upon hypophagic and motor activation response to human/ratCRF (h/rCRF) were investigated. All three antagonists (100 microg intracerebroventricular (i.c.v.)) blocked the effects of h/rCRF (1 microg i.c.v.) upon food intake and body weight change in food-deprived rats. In contrast, alpha-helical CRF-(9-41) and astressin (both at 100 microg i.c.v., but not lower doses), but not D-PheCRF-(12-41) (up to 100 microg i.c.v.), blocked h/rCRF (0.3 microg i.c.v.)-induced motor activation in rats in a familiar environment. The ability of D-PheCRF-(12-41) to block CRF-induced hypophagia, but not motor activation, suggests a selective action of this antagonist upon the behavioural effects of centrally administered h/rCRF.