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GABA(A)R plasticity during pregnancy: relevance to postpartum depression
1Department of Neurology, The David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Neuron
|August 1, 2008
Summary
Pregnancy alters brain GABA(A) receptors (GABA(A)Rs), impacting neuronal inhibition. Genetic changes in GABA(A)R delta subunits in mice caused postpartum depression-like behaviors, treatable with a specific agonist.
Area of Science:
- Neuroscience
- Neuroendocrinology
- Pharmacology
Background:
- Neurosteroid levels fluctuate during the ovarian cycle, influencing neuronal excitability via GABA(A) receptors (GABA(A)Rs).
- Progesterone-derived neurosteroids increase during pregnancy and decline sharply at parturition, potentially affecting GABA(A)Rs postpartum.
Purpose of the Study:
- To investigate the impact of pregnancy and parturition on GABA(A)R-mediated inhibition in mice.
- To examine the role of GABA(A)R delta subunit regulation in maternal behavior and postpartum mood.
Main Methods:
- Assessed tonic and phasic inhibition in pregnant and postpartum mice.
- Utilized genetic mouse models (Gabrd(+/-) and Gabrd(-/-)) lacking GABA(A)R delta subunit regulation.
- Administered a GABA(A)R delta-subunit-selective agonist (THIP) to relevant mouse models.
Main Results:
- Pregnant mice showed decreased tonic and phasic inhibition, linked to GABA(A)R delta and gamma2 subunit downregulation, which normalized postpartum.
- Mice lacking GABA(A)R delta subunit regulation exhibited depression-like and abnormal maternal behaviors, reducing pup survival.
- Treatment with THIP ameliorated these abnormal postpartum behaviors in Gabrd(+/-) mice.
Conclusions:
- GABA(A)R delta subunit regulation is crucial for normal maternal behavior and preventing postpartum depression-like symptoms.
- Gabrd(+/-) and Gabrd(-/-) mice represent a valuable model for studying postpartum depression.
- This model can aid in evaluating therapeutic strategies for postpartum depression.
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