Progesterone regulation of GABA A receptor plasticity in adult rat supraoptic nucleus

Marked plasticity in GABA A receptor signalling occurs in adult oxytocin neurons of the supraoptic nucleus (SON) through the modulation of GABA A receptor α subunits during pregnancy. The present studies were undertaken to examine the potential mechanisms underlying this plasticity. In vivo microdialysis experiments in conscious rats revealed that no significant changes in extracellular GABA concentrations occurred within the SON over the last two days of pregnancy and the time of parturition itself. In situ hybridization studies examined the effects of gonadal steroid manipulation upon the GABA A receptor subunits expressed by SON neurons (α 1 , α 2 , β 2 and γ 2 subunits) and demonstrated that cellular levels of the α 1 subunit were increased following 8 days oestrogen and progesterone treatment. Estrogen alone or allopregnanolone, the progesterone derivative, had no effect on α 1 subunit mRNA expression in the SON. Immunocytochemical experiments demonstrated progesterone receptors in many neural populations but not within the SON of late pregnant rats. These studies indicate that alterations in endogenous GABA release within the SON are unlikely to be responsible for the GABA A receptor plasticity exhibited by oxytocin neurons in late pregnancy. Rather, data demonstrate that the fluctuating concentrations of progesterone during pregnancy act indirectly on SON neurons to modulate α 1 subunit mRNA expression. Together, these experiments provide evidence for the ligand‐independent induction of GABA A receptor plasticity in the adult brain by progesterone.