Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety

Stress. 2005 Dec;8(4):209-19. doi: 10.1080/10253890500504557.


Stress initiates a series of neuronal responses that prepare an organism to adapt to new environmental challenges. However, chronic stress may lead to maladaptive responses that can result in psychiatric syndromes such as anxiety and depressive disorders. Corticotropin-releasing factor (CRF) has been identified as a key neuropeptide responsible for initiating many of the endocrine, autonomic and behavioral responses to stress. The amygdala expresses high concentrations of CRF receptors and is itself a major extrahypothalamic source of CRF containing neurons. Within the amygdala, the basolateral nucleus (BLA) has an important role in regulating anxiety and affective responses. During periods of stress, CRF is released into the amygdala and local CRF receptor activation has been postulated as a substrate for stress-induced alterations in affective behavior. Previous studies have suggested that synaptic plasticity in the BLA contributes to mechanisms underlying long-term changes in the regulation of affective behaviors. Several studies have shown that acute glutamate receptor-mediated activation, by either GABA-mediated disinhibition or CRF-mediated excitation, induces long-term synaptic plasticity and increases the excitability of BLA neurons. This review summarizes some of the data supporting the hypotheses that stress induced plasticity within the amygdala may be a critical step in the pathophysiology of the development of chronic anxiety states. It is further proposed that such a change in the limbic neural circuitry is involved in the transition from normal vigilance responses to pathological anxiety, leading to syndromes such as panic and post-traumatic stress disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Anxiety / etiology*
  • Behavior, Animal*
  • Chronic Disease
  • Corticotropin-Releasing Hormone / physiology*
  • Models, Biological
  • Neural Pathways
  • Neuronal Plasticity / physiology*
  • Rats
  • Stress, Physiological / complications*
  • Synaptic Transmission


  • Corticotropin-Releasing Hormone