The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.
Differential Regulation of Hippocampal Glucocorticoid Receptors mRNA and Fast Feedback: Relevance to Post‐Traumatic Stress Disorder
Open accessAbstract
Hippocampal glucocorticoid receptors (GR and MR) play an important role in glucocorticoid negative feedback. Abnormalities in negative feedback are found in depression and in post‐traumatic stress disorder (PTSD), suggesting that GR and MR might be involved in the pathophysiology of these disorders. Enhanced negative feedback, the PTSD‐specific neuroendocrine abnormality, can be induced in animals using a single prolonged stress (SPS) paradigm (a number of different stressors in one prolonged session, ‘no stress’ interval and a testing session one week later). In the current study, we examined hippocampal GR and MR mRNA distribution in the same animals that exhibited altered negative feedback following the SPS. Seven groups of adult Sprague‐Dawley male rats (seven animals each) were used in two studies, comparing unstressed controls to acutely stressed animals (SPS: 24 h group), SPS animals (seven and 14 days), and SPS+chronic stress animals. GR and MR mRNA distribution across hippocampal subfields was studied using in ‐ situ hybridization with 35 S‐labelled cRNA probes. Acute stress produced down‐regulation of GR and MR mRNA across all hippocampal subfields. Seven days later (SPS‐7 group), there was a differential recovery, with GR mRNA reaching higher than the prestress levels, and MR mRNA remaining down‐regulated. The same differential regulation was present in the 14‐day group. Chronically stressed animals that exhibited normal fast feedback also had normalization in their GR and MR mRNA levels. The MR/GR ratio was decreased only in animals that had enhanced fast feedback. These findings suggest that the increase in GR, in hippocampus is involved in the fast feedback hypersensitivity observed in the SPS animals, and might also underlie enhanced dexamethasone sensitivity found in PTSD. Since differential activation of GR and MR can modulate memory, behavioural responsivity, anxiety and fear, change in MR/GR ratio might also explain other PTSD‐related phenomena.
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“Rats subjected to SPS (SPS rats) show enhanced negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis function in response to glucocorticoid administration (Liberzon et al, 1997(Liberzon et al, , 1999)).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Liberzon et al, 1999
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Pitman, R. K., Rasmusson, A. M., Koenen, K. C., Shin, L. M., Orr, S. P., Gilbertson, M. W., Milad, M. R., & Liberzon, I. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3339 · Cited by 1,529
The biology of fear- and anxiety-related behaviors
Steimer, T. J. (2002) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2002.4.3/tsteimer · Cited by 796
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Korte, S. M. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00002-1 · Cited by 607
The selfish brain: Competition for energy resources
Peters, A., Schweiger, U., Pellerin, L., Hubold, C., Oltmanns, K. M., Conrad, M., Schultes, B., Born, J., & Fehm, H. L. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.03.002 · Cited by 489
Neural circuits mediating stress
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Metadata
- Authors
- Liberzon, López, Flagel, Vázquez, & Young
- Affiliations
- United States Department of Veterans Affairs (US)
- University of Michigan (US)
- ORCID
- López
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 1999-01
- Volume
- 11
- Issue
- 1
- Pages
- 11-17
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W1536317835
- Cited by
- 308
- References
- 37
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 11 · 2022: 11 · 2021: 17 · 2020: 27 · 2019: 24 · 2018: 21 · 2017: 18 · 2016: 18 · 2015: 16 · 2014: 16 · 2013: 11 · 2012: 11
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (5r29mh045232-05)
- National Institute of Mental Health (MH-00427, MH 45232)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- glucocorticoid receptor, mineralocorticoid receptor, hippocampus, glucocorticoid negative feedback, post-traumatic stress disorder, single prolonged stress, chronic stress, receptor mRNA expression, dexamethasone sensitivity, stress recovery
- MeSH terms
- Animals, Depression, Feedback, Gene Expression Regulation, Hippocampus, Male, Receptors, Glucocorticoid, RNA, Messenger, Stress, Physiological, Stress Disorders, Post-Traumatic, Rats, Sprague-Dawley, In Situ Hybridization, Rats
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