Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: A putative post-traumatic stress disorder model
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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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).”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as 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).”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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