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Updated: May 8, 2026

Developing a Rat Model for Bipolar Disorder

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Allopregnanolone and mood disorders.

T Bäckström¹, M Bixo¹, M Johansson¹

¹Umeå Neurosteroid Research Center, Department of Clinical Sciences, University of Umeå, Sweden.

Progress in Neurobiology

|August 28, 2013

Summary

This summary is machine-generated.

Negative mood symptoms in women with Premenstrual Dysphoric Disorder (PMDD) are linked to a paradoxical reaction to allopregnanolone, a progesterone metabolite, acting on the GABA-A receptor system.

Keywords:

Allopregnanolone CNS GABA-A GABA-A receptor modulating steroids GABA-AR GAMS HRt MPA Menstrual cycle OFC PMDD PMS Paradoxical effects Premenstrual dysphoric disorder SEV central nervous system fMRI functional magnetic resonance imaging gamma-butyric-acid-A gamma-butyric-acid-A receptor hormone replacement therapy mPFC medial prefrontal medroxyprogesterone-acetate orbitofrontal cortex premenstrual dysphoric disorder premenstrual syndrome saccadic eye velocity

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Published on: January 3, 2017

Area of Science:

Neuroscience
Endocrinology
Psychiatry

Background:

Certain women experience negative mood symptoms linked to menstrual cycles and hormone treatments.
Premenstrual Dysphoric Disorder (PMDD) is associated with increased negative mood during the luteal phase, correlating with allopregnanolone increases.
This contrasts with the generally mood-enhancing effects of GABA-A receptor modulators.

Purpose of the Study:

To investigate the hypothesis that allopregnanolone, acting on the GABA-A receptor system, provokes mood symptoms in women with PMDD.
To explore the paradoxical effects of GABA-A receptor modulators and their potential link to PMDD mechanisms.

Main Methods:

Analysis of mood symptoms in relation to allopregnanolone serum concentrations.
Functional magnetic resonance imaging (fMRI) to assess amygdala activity.
Evaluation of GABA-A receptor sensitivity to various modulators in patients with PMDD.

Main Results:

Negative mood symptoms severity correlates with allopregnanolone serum concentrations in an inverted U-shaped curve.
Allopregnanolone exhibits paradoxical effects, inducing negative mood at specific concentrations.
Patients with PMDD show altered GABA-A receptor sensitivity, with decreased sensitivity to diazepam and pregnanolone, but increased sensitivity to allopregnanolone.

Conclusions:

Negative mood symptoms in women with PMDD are likely caused by a paradoxical allopregnanolone effect mediated through the GABA-A receptor.
Findings suggest a potential mechanism involving altered GABA-A receptor subunit composition (alpha4 and delta) contributing to anxiogenic effects.