Behavioral effects of central administration of the novel CRF antagonist astressin in rats

Astressin, a novel corticotropin releasing factor (CRF) antagonist, has bee n found to be particularly potent at inhibiting the hypothalamo-pituitary-a drenal axis. The aim of the present study was to determine the effects in r ats of astressin in attenuating the anxiogenic-like response produced by so cial stress and intracerebroventricular (ICV) CRF administration on the ele vated plus-maze, and ICV CRF-induced locomotor activation in the rat. Astre ssin significantly reversed the anxiogenic-like response induced by both so cial stress and ICV rat/ humanCRF (r/hCRF) on the elevated plus-maze, but f ailed to block the effects of r/hCRF-induced locomotor activity in a famili ar environment. When these results were compared to previous studies perfor med with the same paradigms using other CRF antagonists, astressin showed e ffects similar to those of D-PheCRF((12-41)) on plus-maze performance. Howe ver, contrary to alpha-helical CRF(9-41) and D-PheCRF((12-41)), astressin h ad no effect on CRF-induced locomotor activity. These results suggest that astressin may have a unique anti-CRF profile compared to previously tested antagonists.. [Neuropsychopharmacology 22:230-239, 2000] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc..