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

Marked plasticity in GABA(A) receptor signalling occurs in adult oxytocin n eurons of the supraoptic nucleus (SON) through the modulation of GABA(A) re ceptor alpha subunits during pregnancy. The present studies were undertaken to examine the potential mechanisms underlying this plasticity. In vivo mi crodialysis experiments in conscious rats revealed that no significant chan ges in extracellular GABA concentrations occurred within the SON over the l ast two days of pregnancy and the time of parturition itself. In situ hybri dization studies examined the effects of gonadal steroid manipulation upon the GABA(A) receptor subunits expressed by SON neurons (alpha(1), alpha(2), beta(2) and gamma(2) subunits) and demonstrated that cellular levels of th e alpha(1) subunit were increased following 8 days oestrogen and progestero ne treatment. Estrogen alone or allopregnanolone, the progesterone derivati ve, had no effect on alpha(1) subunit mRNA expression in the SON. Immunocyt ochemical experiments demonstrated progesterone receptors in many neural po pulations but not within the SON of late pregnant rats. These studies indic ate that alterations in endogenous GABA release within the SON are unlikely to be responsible for the GABA(A) receptor plasticity exhibited by oxytoci n neurons in late pregnancy. Rather, data demonstrate that the fluctuating concentrations of progesterone during pregnancy act indirectly on SON neuro ns to modulate alpha(1) subunit mRNA expression. Together, these experiment s provide evidence for the ligand-independent induction of GABA(A) receptor plasticity in the adult brain by progesterone.