GABA(A)R plasticity during pregnancy: relevance to postpartum depression.
Fluctuating neurosteroid levels over the ovarian cycle modulate neuronal excitability through effects on GABA(A) receptors (GABA(A)Rs). The large increase in progesterone-derived neurosteroids during pregnancy and their precipitous decline at parturition may have considerable effects on GABA(A)Rs during pregnancy and postpartum. Here we show a significant decrease in tonic and phasic inhibitions in pregnant mice, mediated by a downregulation of GABA(A)R delta and gamma2 subunits, respectively, which rebounds immediately postpartum. Mice which do not exhibit GABA(A)R delta subunit regulation throughout pregnancy (Gabrd(+/-) and Gabrd(-/-)) exhibit depression-like and abnormal maternal behaviors, resulting in reduced pup survival. These abnormal postpartum behaviors were ameliorated in Gabrd(+/-) mice by a GABA(A)R delta-subunit-selective agonist, THIP. We suggest that Gabrd(+/-) and Gabrd(-/-) mice constitute a mouse model of postpartum depression that may be useful for evaluating potential therapeutic interventions.
Maguire
Jamie
J
Department of Neurology, The David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mody
Istvan
I
D000818:Animals; D019052:Depression, Postpartum / Q000235:genetics / Q000378:metabolism* / Q000523:psychology*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D005260:Female; D058787:GABA-A Receptor Antagonists; D008425:Maternal Behavior / Q000502:physiology / Q000523:psychology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*
D058787:GABA-A Receptor Antagonists; C546280:Gabrg2 protein, mouse; D011963:Receptors, GABA-A