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 recept or) subunit mRNAs and polypeptides as well as muscimol-stimulated Cl-3 6(-) uptake were measured in rat cerebral cortex or hippocampus at var ious times during pregnancy and after delivery. RNase protection assay s revealed that the amount of the gamma 2L subunit mRNA decreased prog ressively during pregnancy, in the cerebral cortex and hippocampus, an d then returned to control values around the time of delivery. A simil ar pattern was observed for the alpha 5 subunit mRNA in the cerebral c ortex, 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 mRNA s. 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 amo unt 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-stimulate d Cl-36(-) uptake in cerebral cortical membrane vesicles. Muscimol-ind uced 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(-) upta ke also were reduced. In contrast, the effects of muscimol, allopregna nolone and diazepam were significantly increased, relative to animals in oestrus, after delivery.