Cited by 149Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

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GABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response

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Gunn, Benjamin G., Cunningham, Linda, Mitchell, Scott G., Swinny, Jerome D., Lambert, Jeremy J., Belelli, Delia·2015·Frontiers in Neuroendocrinology

DOI 10.1016/j.yfrne.2014.06.001PMC PMC4349499

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Abstract

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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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
ORCID: Gunn, Benjamin G.
Swinny, Jerome D.
Lambert, Jeremy J.
Belelli, Delia
Venue: Frontiers in Neuroendocrinology
Publisher: Elsevier BV
Published: 2015-01
Volume: 36
Pages: 28-48
ISSN: 0091-3022 (ISSN-L)
DOI: 10.1016/j.yfrne.2014.06.001
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
FWCI: 1.07
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/3.0/ (vor)
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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GABAA receptor-acting neurosteroids: A role in the development and regulation of the stress response

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