Early Post-Stressor Intervention with High-Dose Corticosterone Attenuates Posttraumatic Stress Response in an Animal Model of Posttraumatic Stress Disorder
Received 29 January 2008; received in revised form 25 May 2008; accepted 29 May 2008. published online 21 July 2008.
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.
aMinistry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
bDepartment of Medicine, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
cThe Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv University, Israel
Address reprint requests to Hagit Cohen, Ph.D., Anxiety and Stress Research Unit, Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 4600, Beer-Sheva 84170 Israel
ABSTRACT