Allopregnanolone modulation of HPA axis function in the adult rat

Rationale GABAergic neuronal circuits regulate neuroendo- crine 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 expres- sion of specific GABAA receptor subunits in various brain regions, with consequent changes in receptor function. Objective 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 differ- ences in allopregnanolone levels can influence general resilience. Results The results showed that there is an apparent correla- tion between endogenous levels of brain allopregnanolone and basal and stress-stimulated HPA axis activity. Conclusion 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.