Cited by 252Posttraumatic Stress Disorder ResearchStress Responses and CortisolMemory and Neural Mechanisms

Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: A putative post-traumatic stress disorder model

Kohda, K., Harada, K., Kato, K., Hoshino, A., Motohashi, J., Yamaji, T., Morinobu, S., Matsuoka, N. +1 more·2007·Neuroscience

Abstract

Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experience, and presents with characteristic symptoms, such as intrusive memories, a state of hyperarousal, and avoidance, that endure for years. Single-prolonged stress (SPS) is one of the animal models proposed for PTSD. Rats exposed to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD, and increased expression of glucocorticoid receptor (GR) in the hippocampus. In this study, we characterized further neuroendocrinologic, behavioral and electrophysiological alterations in SPS rats. Plasma corticosterone recovered from an initial increase within a week, and gross histological changes and neuronal cell death were not observed in the hippocampus of the SPS rats. Behavioral analyses revealed that the SPS rats presented enhanced acoustic startle and impaired spatial memory that paralleled the deficits in hippocampal long-term potentiation (LTP) and depression. Contextual fear memory was enhanced in the rats 1 week after SPS exposure, whereas LTP in the amygdala was blunted. Interestingly, blockade of GR activation by administering 17-beta-hydroxy-11-beta-/4-/[methyl]-[1-methylethyl]aminophenyl/-17-alpha-[prop-1-ynyl]estra-4-9-diene-3-one (RU40555), a GR antagonist, prior to SPS exposure prevented potentiation of fear conditioning and impairment of LTP in the CA1 region. Altogether, SPS caused a number of behavioral changes similar to those described in PTSD, which marks SPS as a putative PTSD model. The preventive effects of a GR antagonist suggested that GR activation might play a critical role in producing the altered behavior and neuronal function of SPS rats.

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Crossref · 10.1016/j.neuroscience.2007.05.041

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  • After an undisturbed period of 7 or 14 days, rats exposed to SPS show enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis.

    “Exposure to SPS involves three different stress paradigms and, after an undisturbed period of 7 or 14 days, rats show enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis and an exaggerated acoustic startle response (ASR) (Liberzon et al, 1997;Khan and Liberzon, 2004;Kohda et al, 2007).”
  • After an undisturbed period of 7 or 14 days, rats exposed to SPS show an exaggerated acoustic startle response (ASR).

    “Exposure to SPS involves three different stress paradigms and, after an undisturbed period of 7 or 14 days, rats show enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis and an exaggerated acoustic startle response (ASR) (Liberzon et al, 1997;Khan and Liberzon, 2004;Kohda et al, 2007).”

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Authors
Kohda, K., Harada, K., Kato, K., Hoshino, A., Motohashi, J., Yamaji, T., Morinobu, S., Matsuoka, N., & Kato, N.
Affiliations
  • The University of Tokyo (JP)
  • University of Kochi (JP)
  • Hiroshima University (JP)
Corresponding author
Kohda, K.
Venue
Neuroscience
Publisher
Elsevier BV
Published
2007-08
Volume
148
Issue
1
Pages
22-33
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2021393321
Cited by
252
References
83
Citations by year
2026: 7 · 2025: 9 · 2024: 5 · 2023: 13 · 2022: 7 · 2021: 12 · 2020: 10 · 2019: 10 · 2018: 19 · 2017: 21 · 2016: 18 · 2015: 15 · 2014: 18 · 2013: 14 · 2012: 19
FWCI
14.49
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
post-traumatic stress disorder, single prolonged stress, glucocorticoid receptor, glucocorticoid receptor antagonist, hippocampus, amygdala, long-term potentiation, contextual fear memory, acoustic startle response, spatial memory, hypothalamic-pituitary-adrenal axis, corticosterone, fear conditioning, CA1 region, animal model of PTSD
MeSH terms
Amygdala, Animals, Anxiety Disorders, Avoidance Learning, Corticosterone, Disease Models, Animal, Fear, Hippocampus, Hypothalamo-Hypophyseal System, Male, Memory, Memory Disorders, Nerve Degeneration, Phenotype, Receptors, Glucocorticoid, Reflex, Abnormal, Reflex, Startle, Stress Disorders, Post-Traumatic, Stress, Psychological, Mifepristone, Cell Death, Rats, Sprague-Dawley, Long-Term Potentiation, Rats

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