Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior

Neuroscience. 2004;128(4):667-73. doi: 10.1016/j.neuroscience.2004.07.013.


The hippocampus and amygdala are important components of the neural circuitry mediating stress responses. While structural plasticity in the hippocampus may mediate cognitive aspects of behavioral impairments caused by severe stress, changes in the amygdala are more likely to contribute to the affective aspects of stress disorders. Recent reports have identified cellular and molecular correlates of stress-induced amygdaloid plasticity that may underlie anxiety. Hence, we examined the impact of chronic stress, in terms of its duration, at the cellular and behavioral levels in rats. We found that, even after 21 days of stress-free recovery, animals exposed to chronic immobilization stress (CIS) continue to exhibit enhanced anxiety, as manifested by a significant reduction in open-arm exploration and risk-assessment behavior in the elevated plus-maze. At the cellular level, we tested if CIS-induced dendritic remodeling in the amygdala is also as long-lasting as enhanced anxiety after 21 days of recovery. Indeed, long-lasting facilitation of CIS-induced anxiety is accompanied by a persistent increase in dendritic arborization of basolateral amygdala (BLA) spiny neurons. Moreover, CIS-induced BLA hypertrophy is distinct from hippocampal CA3 atrophy, which is reversible within the same period of stress-free recovery. These findings on persistent dendritic remodeling in the amygdala, in addition to highlighting important differences with hippocampal structural plasticity, may provide a cellular basis for examining anxiety and mood disorders triggered by chronic stress.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / pathology*
  • Animals
  • Anxiety / etiology*
  • Behavior, Animal
  • Cell Size*
  • Dendritic Spines / pathology
  • Disease Models, Animal
  • Hippocampus / cytology
  • Hippocampus / pathology
  • Hypertrophy / pathology
  • Male
  • Maze Learning / physiology
  • Neurons / pathology*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Restraint, Physical / methods
  • Stress, Physiological* / pathology
  • Stress, Physiological* / physiopathology
  • Time Factors