GABAA receptor-acting neurosteroids: a role in the development and regulation of the stress response
Open accessAbstract
Regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity by stress is a fundamental survival mechanism and HPA-dysfunction is implicated in psychiatric disorders. Adverse early life experiences, e.g. poor maternal care, negatively influence brain development and programs an abnormal stress response by encoding long-lasting molecular changes, which may extend to the next generation. How HPA-dysfunction leads to the development of affective disorders is complex, but may involve GABAA receptors (GABAARs), as they curtail stress-induced HPA axis activation. Of particular interest are endogenous neurosteroids that potently modulate the function of GABAARs and exhibit stress-protective properties. Importantly, neurosteroid levels rise rapidly during acute stress, are perturbed in chronic stress and are implicated in the behavioural changes associated with early-life adversity. We will appraise how GABAAR-active neurosteroids may impact on HPA axis development and the orchestration of the stress-evoked response. The significance of these actions will be discussed in the context of stress-associated mood disorders.
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Allopregnanolone enhances negative feedback on the HPA axis.
“and enhance the negative feedback on the HPA axis (21, 22).”
From Higher Circulating Cortisol in the Follicular vs. Luteal Phase of the Menstrual Cycle: A Meta-Analysis (2020) · cites this paper as [22]
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- Authors
- Gunn, B. G., Cunningham, L., Mitchell, S. G., Swinny, J. D., Lambert, J. J., & Belelli, D.
- Affiliations
- University of Dundee (GB)
- University of Portsmouth (GB)
- Corresponding author
- Belelli, Delia
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 36
- Pages
- 28-48
- ISSN
- 0091-3022 (ISSN-L)
- PMC
- PMC4349499
- OpenAlex
- W2113668852
- Cited by
- 149
- References
- 317
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 8 · 2023: 10 · 2022: 18 · 2021: 8 · 2020: 16 · 2019: 20 · 2018: 14 · 2017: 16 · 2016: 7 · 2015: 11 · 2014: 6
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Frontiers in Neuroendocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- Wellbeing of Women (RG1265)
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- GABAA receptor, neurosteroids, hypothalamic-pituitary-adrenal axis, stress response, childhood adversity, maternal care, chronic stress, stress-protective effect, mood disorders, intergenerational transmission
- MeSH terms
- Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Receptors, GABA-A, Stress, Psychological, Neurotransmitter Agents
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