| First Author | Maguire J | Year | 2008 |
| Journal | Neuron | Volume | 59 |
| Issue | 2 | Pages | 207-13 |
| PubMed ID | 18667149 | Mgi Jnum | J:145475 |
| Mgi Id | MGI:3834796 | Doi | 10.1016/j.neuron.2008.06.019 |
| Citation | Maguire J, et al. (2008) GABA(A)R plasticity during pregnancy: relevance to postpartum depression. Neuron 59(2):207-13 |
| abstractText | 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. |
