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Early Post-Stressor Intervention with High-Dose Corticosterone Attenuates Posttraumatic Stress Response in an Animal Model of Posttraumatic Stress Disorder

  • Hagit Cohen
    Correspondence
    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
    Affiliations
    Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Michael A. Matar
    Affiliations
    Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Dan Buskila
    Affiliations
    Department of Medicine, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Zeev Kaplan
    Affiliations
    Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Joseph Zohar
    Affiliations
    The Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv University, Israel
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      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.

      Key Words

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