GABA(A)R plasticity during pregnancy: relevance to postpartum depression

Neuron. 2008 Jul 31;59(2):207-13. doi: 10.1016/j.neuron.2008.06.019.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Depression, Postpartum / genetics
  • Depression, Postpartum / metabolism*
  • Depression, Postpartum / psychology*
  • Down-Regulation / genetics
  • Down-Regulation / physiology
  • Female
  • GABA-A Receptor Antagonists
  • Maternal Behavior / physiology
  • Maternal Behavior / psychology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy
  • Pregnancy Complications / genetics
  • Pregnancy Complications / metabolism*
  • Pregnancy Complications / psychology
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / physiology*


  • GABA-A Receptor Antagonists
  • Gabrg2 protein, mouse
  • Receptors, GABA-A