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

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

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
Venue
Frontiers in Neuroendocrinology
Publisher
Elsevier BV
Published
2015-01
Volume
36
Pages
28-48
ISSN
0091-3022 (ISSN-L)
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
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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