Early post-stressor intervention with high-dose corticosterone attenuates posttraumatic stress response in an animal model of posttraumatic stress disorder

Biol Psychiatry. 2008 Oct 15;64(8):708-717. doi: 10.1016/j.biopsych.2008.05.025. Epub 2008 Jul 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Cats
  • Corticosterone / administration & dosage
  • Corticosterone / blood*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology*
  • Stress Disorders, Post-Traumatic / blood
  • Stress Disorders, Post-Traumatic / etiology
  • Stress Disorders, Post-Traumatic / prevention & control*
  • Stress, Psychological / blood
  • Stress, Psychological / complications*
  • Time Factors

Substances

  • Corticosterone