Molecular and functional adaptation of the GABA(A) receptor complex during pregnancy and after delivery in the rat brain

The abundance of gamma-aminobutyric acid receptor type A (GABAA receptor) subunit mRNAs and polypeptides as well as muscimol-stimulated Cl-36(-) uptake were measured in rat cerebral cortex or hippocampus at various times during pregnancy and after delivery. RNase protection assays revealed that the amount of the gamma 2L subunit mRNA decreased progressively during pregnancy, in the cerebral cortex and hippocampus, and then returned to control values around the time of delivery. A similar pattern was observed for the alpha 5 subunit mRNA in the cerebral cortex, whereas no significant changes were apparent for alpha 1, alpha 2, alpha 3, alpha 4, beta 1, beta 2, beta 3 and gamma 2S subunit mRNAs. The amounts of gamma 2 and alpha 1 proteins in the cerebral cortex were measured by immunoblot analysis; whereas the abundance of gamma 2 protein decreased during pregnancy, no change was detected in the amount of alpha 1 protein. Evaluation for functional significance of the down-regulated gamma 2 and alpha 5 subunit was made by determining the GABAA receptor function assessed by measurement of muscimol-stimulated Cl-36(-) uptake in cerebral cortical membrane vesicles. Muscimol-induced Cl-36(-) uptake was markedly reduced during of pregnancy compared with rats in oestrus. At this same time, the potentiating effects of diazepam and allopregnanolone on muscimol stimulation of Cl-36(-) uptake also were reduced. In contrast, the effects of muscimol, allopregnanolone and diazepam were significantly increased, relative to animals in oestrus, after delivery.