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

Neuroactive steroids such as 3alpha,5alpha-THP are reduced metabolites of progesterone and are considered to play an important physiological role to locally modulate neuronal excitability by "fine-tuning" the action of GABA acting at GABA(A) receptors (GABA(A)-Rs). In different brain regions, such as the hippocampus, different subpopulations of nerve cells exhibit two components of inhibitory GABAergic transmission: a phasic component mediated by synaptic GABA(A)-Rs, and a tonic component mediated by "ambient" GABA acting at extrasynaptic GABA(A)-Rs mainly containing the delta subunit and endowed with a higher sensitivity to neuroactive steroids compared to synaptic receptors. It is also well accepted that fluctuations in brain neuroactive steroid levels may result in plastic changes of GABA(A)-Rs. In this article we review some of our results obtained with the model of pregnancy in rats. Pregnancy, in fact, is characterized by a marked and progressive increase in plasma and brain levels of neuroactive steroids which could contribute to changes in mood, anxiety as well as other psychiatric conditions. Such elevation in brain neuroactive steroid concentrations during pregnancy, in turn, is accompanied by alterations in both gene expression and function of synaptic and extrasynaptic GABA(A)-Rs in the hippocampus as well as other areas.