Circadian activity of the hypothalamic-pituitary-adrenal axis is differentially affected in the rat chronic mild stress model of depression
Open accessAbstract
The altered activity of the hypothalamic-pituitary-adrenal (HPA) axis is often observed in stress-related disorders. According to the literature, about 60% of patients with major depressive disorder elicit high levels of cortisol. It is still unclear why high cortisol levels are not observed in all patients. In this study, we used the chronic mild stress (CMS) rat model of depression, which is based on continuous exposure to unpredictable stressors, to track longitudinal changes in HPA function using fecal corticosterone metabolites (FCM) as a read out. The dexamethasone suppression test was used to assess negative feedback inhibition of the HPA axis. Our results show (1) a disturbance in diurnal corticosterone rhythm measured as fluctuations of the diurnal FCM peak, (2) differences in corticosterone levels between stress-susceptible and stress-resilient animals, (3) recovery of diurnal corticosterone rhythm after 8 weeks of CMS, and (4) alterations in sensitivity to dexamethasone in negative feedback regulation of corticosterone secretion during the time course of CMS. Thus, a disruption of HPA axis circadian rhythmicity coincides with the initial state in the development of depression-like behavior. This chronobiological abnormality, as well as the hypersecretion of corticosterone, is state, rather than trait, dependent.
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Acute and chronic physical and/or psychological stress affects the sleep centers of the brain.
“Numerous human and animal studies suggest that acute and chronic physical and/or psychological stress affects the sleep centers of the brain (356–363).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [360]
The Discussion reports that chronic mild stress altered circadian HPA-axis activity in rats, not that it affected the brain’s sleep centers. Searches for sleep-center and sleep-disturbance terms found no passage in our copy addressing that claim; the Introduction discusses cortisol rhythms around waking but does not establish an effect on sleep centers. (LLM, conf=0.75)
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Hagenauer, M. H., O’Connor, A. M., Forrester, L. C. T., Maras, P. M., Arakawa, K., Khalil, H., Richardson, E., Hebda‐Bauer, E. K., Rob, F. I., Sannah, Y., et al. (2024) · Figshare · doi:10.6084/m9.figshare.24085524
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- Authors
- Christiansen, S., Bouzinova, E. V., Palme, R., & Wiborg, O.
- Affiliations
- Aarhus University Hospital (DK)
- University of Veterinary Medicine Vienna (AT)
- Corresponding author
- Bouzinova, E. V.
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2012-02-23
- Volume
- 15
- Issue
- 6
- Pages
- 647-657
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- OpenAlex
- W2159609211
- Semantic Scholar
- 0221d46d63b4381f38076ad58f10657a451c92b2
- Cited by
- 55
- References
- 42
- Citations by year
- 2025: 1 · 2024: 4 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 8 · 2012: 4
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- hypothalamic-pituitary-adrenal axis, chronic mild stress, depression, circadian rhythm, fecal corticosterone metabolites, dexamethasone suppression test, negative feedback regulation, stress resilience, stress vulnerability, cortisol hypersecretion, rat model of depression
- MeSH terms
- Animals, Circadian Rhythm, Corticosterone, Depression, Dexamethasone, Feces, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Rats
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