title: Effects of a non-peptide CRF antagonist (DMP696) on the behavioral and endocrine sequelae of maternal separation.
abstract: We examined whether blockade of corticotropin-releasing factor (CRF) receptors by a non-peptide CRF antagonist (DMP696) would attenuate the stress hyper-responsiveness that occurs in response to maternal separation. In a social interaction test as well as the elevated plus maze, adult male rats, which had been maternally separated as infants, displayed more anxiety-like behavior compared with handled rats. DMP696 increased social interaction in both groups. In the elevated plus maze however, DMP696 significantly increased open arm time in the maternally separated rats but not in the handled group whereas chlordiazepoxide increased open arm time in both groups. DMP696 also appeared to block stress-induced ACTH secretion more readily in the maternally separated group compared with the handled rats. These observations suggest that CRF antagonists are particularly effective in animals that are hyper-responsive to stress and may therefore have utility in the treatment of anxiety and affective disorders where CRF has been implicated.
authors.affiliation: CNS Diseases Research, DuPont Pharmaceuticals Company, Wilmington, DE 19850, USA.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Maciag
authors.forename: Gersham
authors.initials: G
authors.lastname: Dent
authors.forename: Paul
authors.initials: P
authors.lastname: Gilligan
authors.forename: Liqi
authors.initials: L
authors.lastname: He
authors.forename: Krista
authors.initials: K
authors.lastname: Dowling
authors.forename: Tracey
authors.initials: T
authors.lastname: Ko
authors.forename: Seymour
authors.initials: S
authors.lastname: Levine
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002707:Chlordiazepoxide / Q000494:pharmacology; D005260:Female; D006234:Handling, Psychological; D008297:Male; D008426:Maternal Deprivation; D018782:Maze Learning / Q000502:physiology; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D013315:Stress, Psychological / Q000097:blood; D014227:Triazines / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; C404928:DMP 696; D011720:Pyrazoles; D018019:Receptors, Corticotropin-Releasing Hormone; D014227:Triazines; D002707:Chlordiazepoxide; D000324:Adrenocorticotropic Hormone