Glucocorticoids protect against the delayed behavioral and cellular effects of acute stress on the amygdala

Biol Psychiatry. 2012 Sep 15;72(6):466-75. doi: 10.1016/j.biopsych.2012.04.008. Epub 2012 May 8.


Background: A single episode of acute immobilization stress has previously been shown to trigger a delayed onset of anxiety-like behavior and spinogenesis in the basolateral amygdala (BLA) of rats. Spurred on by a seemingly paradoxical observation in which even a modest increase in corticosterone (CORT), caused by a single vehicle injection before stress, could dampen the delayed effects of stress, we hypothesized a protective role for glucocorticoids against stress.

Methods: We tested this hypothesis by analyzing how manipulations in CORT levels modulate delayed increase in anxiety-like behavior of rats on the elevated plus-maze 10 days after acute stress. We also investigated the cellular correlates of different levels of anxiety under different CORT conditions by quantifying spine density on Golgi-stained BLA principal neurons.

Results: CORT in drinking water for 12 hours preceding acute stress prevented delayed increase in anxiety rather than exacerbating it. Conversely, vehicle injection failed to prevent the anxiogenic effect of stress in bilaterally adrenalectomized rats. However, when CORT was restored in adrenalectomized rats by injection, the delayed anxiogenic effect of stress was once again blocked. Finally, high and low anxiety states were accompanied by high and low levels of BLA spine density.

Conclusions: Our findings suggest that the presence of elevated levels of CORT at the time of acute stress confers protection against the delayed enhancing effect of stress on BLA synaptic connectivity and anxiety-like behavior. These observations are consistent with clinical reports on the protective effects of glucocorticoids against the development of posttraumatic symptoms triggered by traumatic stress.

Publication types

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

MeSH terms

  • Adrenalectomy / adverse effects
  • Amygdala / anatomy & histology
  • Amygdala / drug effects*
  • Analysis of Variance
  • Animals
  • Anxiety / drug therapy*
  • Corticosterone / metabolism
  • Corticosterone / pharmacology*
  • Corticosterone / therapeutic use
  • Dendritic Spines / drug effects*
  • Dendritic Spines / physiology
  • Disease Models, Animal
  • Glucocorticoids / metabolism
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Male
  • Rats
  • Rats, Wistar
  • Restraint, Physical
  • Stress Disorders, Post-Traumatic
  • Stress, Psychological / physiopathology*


  • Glucocorticoids
  • Corticosterone