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The role of ovarian hormone-derived neurosteroids on the regulation of GABAA receptors in affective disorders

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Abstract

Rationale

Neuroactive derivatives of steroid hormones, neurosteroids, can act on GABAA receptors (GABAARs) to potentiate the effects of GABA on these receptors. Neurosteroids become elevated to physiologically relevant levels under conditions characterized by increased steroid hormones. There is considerable evidence for plasticity of GABAARs associated with altered levels of neurosteroids which may counteract the fluctuations in the levels of these allosteric modulators.

Objectives

The objective of this review is to summarize the current literature on GABAAR plasticity under conditions characterized by alterations in neurosteroid levels, such as over the estrous cycle, during puberty, and throughout pregnancy and the postpartum period.

Results

The expression of specific GABAAR subunits is altered over the estrous cycle, at puberty, and throughout pregnancy and the postpartum period. Inability to regulate δ subunit-containing GABAARs throughout pregnancy and the postpartum period is associated with depression-like behavior restricted to the postpartum period.

Conclusions

GABAAR plasticity associated with alterations in neurosteroid levels represents a homeostatic compensatory mechanism to maintain an ideal level of inhibition to offset the potentiating effects of neurosteroids on GABAergic inhibition. Failure to properly regulate GABAARs under conditions of altered neurosteroid levels may increase vulnerability to mood disorders, such as premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and postpartum depression.

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Acknowledgments

J.M. and G.M. are supported by NIH grant, R01 NS073574 (J.M.). G.M. was also supported by a postdoctoral fellowship from the Epilepsy Foundation. The authors acknowledge the contributions of Robert H. (Bob) Purdy, to whom this special issue of Psychopharmacology is dedicated, to field of neurosteroids and GABAA receptor function.

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  1. Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, SC205, Boston, MA, 02111, USA

    Georgina MacKenzie & Jamie Maguire

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  1. Georgina MacKenzie
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  2. Jamie Maguire
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Correspondence to Jamie Maguire.

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MacKenzie, G., Maguire, J. The role of ovarian hormone-derived neurosteroids on the regulation of GABAA receptors in affective disorders. Psychopharmacology 231, 3333–3342 (2014). https://doi.org/10.1007/s00213-013-3423-z

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