GABA(A)receptor function and gene expression during pregnancy and postpartum

Neuroactive steroids such as 3α-hydroxy-5α-pregnan-20-one (3α,5α-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 γ-aminobutyric acid (GABA) at GABAA receptors. Fluctuations in the concentrations of neuroactive steroids in the brain are also thought to contribute to GABAA receptor plasticity. We here review results from our laboratory related to the regulation of GABAA 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 GABAA receptor subunits and the function of extrasynaptic GABAA receptors in the hippocampus.