Plasticity and function of extrasynaptic GABA(A) receptors during pregnancy and after delivery.

Neuroactive steroids such as 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) are reduced metabolites of progesterone and are thought to play an important physiological role in local modulation of neuronal excitability by "fine-tuning" the action of gamma-aminobutyric acid (GABA) at GABA(A) receptors. Fluctuations in the concentrations of neuroactive steroids in the brain are also thought to contribute to GABA(A) receptor plasticity. We here review results from our laboratory related to the regulation of GABA(A) receptor function and plasticity by changes in the levels of neuroactive steroids during pregnancy and after delivery in rats. Pregnancy is characterized by marked and progressive increases in the plasma and brain concentrations of neuroactive steroids, which are implicated in the changes in mood, anxiety, and other psychiatric states associated with this condition. We have shown that the increases in the brain levels of neuroactive steroids during pregnancy are causally related to changes in the expression of specific GABA(A) receptor subunits and the function of extrasynaptic GABA(A) receptors in the hippocampus.