title: Stress-restress: effects on ACTH and fast feedback.
abstract: Glucocorticoid secretion is tightly regulated by negative feedback. Glucocorticoid feedback has been found to be altered in depression and post-traumatic stress disorder (PTSD). While hyposensitive glucocorticoid feedback has been found in depression, hypersensitive or enhanced negative feedback was described in PTSD. Enhanced negative feedback, can be seen as a sensitization of the inhibitory elements of HPA axis, and stress-restress or time dependent sensitization (TDS) model, has been suggested as an animal model for PTSD. We have studied the effects of this model on the HPA axis to determine whether it will produce increased sensitivity to negative feedback as found in PTSD patients. Adult Sprague-Dawley male rats were exposed to a single session of prolonged stress (restraint followed by a forced swim and exposure to ether vapors) and briefly restressed 7 days later. The effects of single prolonged stress on plasma ACTH and corticosterone responses (0, 5, and 30 min) and on glucocorticoid fast feedback (cortisol vs. saline pretreatment) were assessed in two studies. Animals exposed to single prolonged stress showed enhanced negative feedback in comparison to naive animals (F = 4.6371, df = 3, p = .0107), but there was no difference in ACTH or corticosterone responses during the restress. Pretreatment with cortisol, in the first stress session, did not prevent the development of the enhanced fast feedback when restressed. This can be seen as a sensitization of the inhibitory elements of HPA axis, suggesting that stress-restress paradigm might serve as a good animal model for HPA abnormalities found in PTSD patients.
authors.affiliation: Psychiatry Department, University of Michigan, Ann Arbor 48109, USA.
authors.forename: I
authors.initials: I
authors.lastname: Liberzon
authors.forename: M
authors.initials: M
authors.lastname: Krstov
authors.forename: E A
authors.initials: EA
authors.lastname: Young
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005246:Feedback / Q000502:physiology*; D006854:Hydrocortisone / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007118:Immunoassay; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000503:physiopathology*; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*
chemical_list: D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone