Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress

Neuropsychopharmacology. 2016 Jan;41(1):45-57. doi: 10.1038/npp.2015.224. Epub 2015 Aug 6.

Abstract

Fear promotes adaptive responses to threats. However, when the level of fear is not proportional to the level of threat, maladaptive fear-related behaviors characteristic of anxiety disorders result. Post-traumatic stress disorder develops in response to a traumatic event, and patients often show sensitized reactions to mild stressors associated with the trauma. Stress-enhanced fear learning (SEFL) is a rodent model of this sensitized responding, in which exposure to a 15-shock stressor nonassociatively enhances subsequent fear conditioning training with only a single trial. We examined the role of corticosterone (CORT) in SEFL. Administration of the CORT synthesis blocker metyrapone prior to the stressor, but not at time points after, attenuated SEFL. Moreover, CORT co-administered with metyrapone rescued SEFL. However, CORT alone without the stressor was not sufficient to produce SEFL. In these same animals, we then looked for correlates of SEFL in terms of changes in excitatory receptor expression. Western blot analysis of the basolateral amygdala (BLA) revealed an increase in the GluA1 AMPA receptor subunit that correlated with SEFL. Thus, CORT is permissive to trauma-induced changes in BLA function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Acute Disease
  • Animals
  • Basolateral Nuclear Complex / metabolism*
  • Basolateral Nuclear Complex / pathology
  • Corticosterone / metabolism
  • Fear / physiology*
  • Fear / psychology
  • Humans
  • Stress Disorders, Post-Traumatic / metabolism*
  • Stress Disorders, Post-Traumatic / pathology
  • Stress Disorders, Post-Traumatic / psychology
  • Stress, Psychological / metabolism
  • Stress, Psychological / pathology
  • Stress, Psychological / psychology

Substances

  • Corticosterone