Oxytocin Regulates Neurosteroid Modulation of GABAAReceptors in Supraoptic Nucleus around Parturition

Abstract

In this study, we investigate how neurosteroid sensitivity of GABA_Areceptors (GABA_ARs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABA_ARs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABA_ARs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABA_ARs from a neurosteroid-sensitive mode toward a condition in which the receptors are not sensitive. This indicates that there may be an inverse causal relationship between the extent to which the GABA_AR or one of its interacting proteins is phosphorylated and the neurosteroid sensitivity of the GABA_AR. Neurosteroid sensitivity was not affected by changes in subunit composition of GABA_ARs known to occur concurrently in these cells.