Allopregnanolone modulation of HPA axis function in the adult rat

Abstract

GABAergic neuronal circuits regulate neuroendocrine stress response, and the most potent positive endogenous modulator of GABAA receptor function is allopregnanolone. This neurosteroid acts in a nongenomic manner to selectively increase the inhibitory signal meditated by GABAA receptors; in addition, it also induces long-lasting changes in the expression of specific GABAA receptor subunits in various brain regions, with consequent changes in receptor function. The objective of this review is to summarize our findings on emotional state and stress responsiveness in three animal models in which basal brain concentrations of allopregnanolone differ. It is postulated that individual differences in allopregnanolone levels can influence general resilience. The results showed that there is an apparent correlation between endogenous levels of brain allopregnanolone and basal and stress-stimulated HPA axis activity. The relationship between endogenous brain levels of allopregnanolone and HPA axis activity and function sustains the therapeutic potential of this neurosteroid for the treatment of stress-associated disorders.