title: Early post-stressor intervention with high-dose corticosterone attenuates posttraumatic stress response in an animal model of posttraumatic stress disorder.
abstract: BACKGROUND
  The therapeutic value of corticosteroids in the aftermath of traumatic experience has been questioned. We used an animal model of posttraumatic stress disorder (PTSD) to assess long-term behavioral effects of a single administration of various doses of corticosterone (CORT), administered immediately after exposure to psychogenic stress.
  
  
  METHODS
  Animals were exposed to predator scent stress and treated 1 hour later with various doses of CORT or saline. The outcome measures included behavior in an elevated plus-maze (EPM) and acoustic startle response (ASR) 30 days after the initial exposure and freezing behavior upon exposure to a trauma-related cue on day 31. Pre-set cut-off behavioral criteria (CBC) classified exposed animals according to behavioral responses in EPM and ASR paradigms as those with "extreme behavioral response," "minimal behavioral response," or "intermediate response." Non-spatial memory task and 24-hour locomotor activity were assessed immediately after injection with CORT or vehicle.
  
  
  RESULTS
  Early treatment with high-dose CORT reduced the prevalence of PTSD-like behavioral responses relative to saline-control treatment. Cue-induced freezing was significantly lower in the high-dose CORT-treated group. Lower doses of CORT significantly increased anxiety-like behavior, mean startle amplitude, and prevalence of PTSD-like behavioral disruptions, compared with saline-control treatment. The attenuated cue-responsiveness and impaired performance on a memory task imply that one key factor in this effect is the disruption of traumatic memory consolidation.
  
  
  CONCLUSIONS
  Single treatment with high-dose CORT immediately after stressful exposure reduces the prevalence rate of extreme behavioral disruption 30 days later. Corticosterone might disrupt the consolidation of aversive or fearful memories.
authors.affiliation: Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: hagitc@bgu.ac.il.
authors.forename: Hagit
authors.initials: H
authors.lastname: Cohen
authors.affiliation: Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matar
authors.affiliation: Department of Medicine, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Buskila
authors.affiliation: Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Kaplan
authors.affiliation: The Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv University, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zohar
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D002415:Cats; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000097:blood / Q000150:complications*; D013997:Time Factors
chemical_list: D003345:Corticosterone