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

Benjamin G. Gunn, Linda Cunningham, Scott Mitchell, Jerome D. Swinny, Jeremy J. Lambert, Delia Belelli

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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 behavioral 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.

Original languageEnglish
Pages (from-to)28-48
JournalFrontiers in Neuroendocrinology
Early online date12 Jun 2014
Publication statusPublished - 1 Jan 2015


  • RCUK
  • MR/K 500896/1


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