Behavioral effects of central administration of the novel CRF antagonist astressin in rats.
Astressin, a novel corticotropin releasing factor (CRF) antagonist, has been found to be particularly potent at inhibiting the hypothalamo-pituitary-adrenal axis. The aim of the present study was to determine the effects in rats of astressin in attenuating the anxiogenic-like response produced by social stress and intracerebroventricular (ICV) CRF administration on the elevated plus-maze, and ICV CRF-induced locomotor activation in the rat. Astressin significantly reversed the anxiogenic-like response induced by both social stress and ICV rat/humanCRF (r/hCRF) on the elevated plus-maze, but failed to block the effects of r/hCRF-induced locomotor activity in a familiar environment. When these results were compared to previous studies performed with the same paradigms using other CRF antagonists, astressin showed effects similar to those of D-PheCRF(12-41) on plus-maze performance. However, contrary to alpha-helicalCRF(9-41) and D-PheCRF(12-41), astressin had no effect on CRF-induced locomotor activity. These results suggest that astressin may have a unique anti-CRF profile compared to previously tested antagonists.
Spina
M G
MG
Institute for Medical Neurobiology, Otto-von-Guericke University, Magdeburg, Germany.
Basso
A M
AM
Zorrilla
E P
EP
Heyser
C J
CJ
Rivier
J
J
Vale
W
W
Merlo-Pich
E
E
Koob
G F
GF
D000374:Aggression; D000595:Amino Acid Sequence; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013315:Stress, Psychological
D010446:Peptide Fragments; D011994:Recombinant Proteins; C104416:astressin; D003346:Corticotropin-Releasing Hormone