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Cited by 237Stress Responses and CortisolMemory and Neural MechanismsNeuropeptides and Animal Physiology

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

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Shekhar, Anantha, Truitt, William, Rainnie, Donald, Sajdyk, Tammy·2005·Stress
DOI 10.1080/10253890500504557
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Abstract

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.

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Crossref · 10.1080/10253890500504557

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  • This suggests a mechanism that might produce pathological amygdala activity in depression.

    “Notably, repeated stress results in hyperexcitability in the BLA in rodents (Shekhar et al, 2005;Vyas et al, 2006) suggesting a mechanism that might produce pathological amygdala activity in depression.”

    From Neurocircuitry of Mood Disorders (2010) · cites this paper as Shekhar et al, 2005

    In “Proposed intrinsic BLA circuit regulating anxiety responses” (page unavailable), the paper proposes that repeated activation during chronic stress could reduce inhibition in the BLA, making it more responsive. “Internal circuitry of BLA” (page unavailable) reports lasting facilitation after repeated experimental disruption of BLA inhibition, but does not establish that repeated stress itself results in BLA hyperexcitability in rodents. The proposed link to depression is the citing authors’ inference, not a finding attributed to this source. (LLM, conf=0.84)

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  • Repeated stress results in hyperexcitability in the BLA in rodents.

    “Notably, repeated stress results in hyperexcitability in the BLA in rodents (Shekhar et al, 2005;Vyas et al, 2006)”

    From Neurocircuitry of Mood Disorders (2010) · cites this paper as Shekhar et al, 2005

    In “Proposed intrinsic BLA circuit regulating anxiety responses” (page not available), the paper says chronic stress could reduce inhibition in BLA circuitry after repeated activation. “Internal circuitry of BLA” reports long-term synaptic facilitation after repeated disruption of BLA inhibition, including evidence from rats. These passages support increased BLA excitability as a plausible mechanism, but do not establish that repeated stress itself reliably produces hyperexcitability in rodents. (LLM, conf=0.86)

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  • Repeated stress results in hyperexcitability states in the BLA in rodents, although whether the mechanisms underlying these changes involve changes in afferent modulation of the amygdala or alterations in synaptic plasticity have not been established.

    “Notably, repeated stress results in hyperexcitability states in the BLA in rodents, although whether the mechanisms underlying these changes involve changes in afferent modulation of the amygdala or alterations in synaptic plasticity have not been established (Shekhar et al. 2005; Vyas et al. 2006).”

    From Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression (2008) · cites this paper as Shekhar et al. 2005

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Research works printed but not linked: 3

  1. [56]56. Gray J. 1982. The neuropsychology of anxiety: An inquiry into the function of the septohippocampal system 10. Oxford: Oxford University Press. p 155 -168.
  2. [119]119. Price JL, Amaral DG. 1987. The limbic region II: The amygdaloid complex. In: Bjorklund A, Hokfelt TH, Swanson LW, editors. Handbook of chemical neruoanatomy. Amsterdam: Elsevier. p 279-388.
  3. [120]120. Price LH, Barr LC, Goodman WK. 1995. Pharmacological challenges in anxiety disorder. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: The fourthe generation of progression. New York: Raven Press. p 1311-1323.

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Authors
Shekhar, A., Truitt, W., Rainnie, D., & Sajdyk, T.
Affiliations
  • Indiana University School of Medicine (US)
  • Emory University (US)
Corresponding author
Shekhar, Anantha
ORCID
Venue
Stress
Publisher
Informa UK Limited
Published
2005-01
Volume
8
Issue
4
Pages
209-219
ISSN
  • 1025-3890 (ISSN-L)
  • 1607-8888
DOI
10.1080/10253890500504557
OpenAlex
W2028934136
Cited by
237
References
168
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 6 · 2019: 10 · 2018: 11 · 2017: 10 · 2016: 8 · 2015: 8 · 2014: 18 · 2013: 20 · 2012: 12
FWCI
5.88
Type
journal article
Language
en
Open access
Locations
  • Stress (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (R01-MH52619, R01MH052619, R01MH065702)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
chronic anxiety, corticotropin-releasing factor, chronic stress, basolateral amygdala, synaptic plasticity, CRF receptors, glutamate receptor activation, limbic system, panic disorder, post-traumatic stress disorder
MeSH terms
Amygdala, Animals, Anxiety, Behavior, Animal, Chronic Disease, Corticotropin-Releasing Hormone, Models, Biological, Neural Pathways, Synaptic Transmission, Neuronal Plasticity, Stress, Physiological, Rats

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