The role of neuroactive steroids in ethanol/stress interactions: proceedings of symposium VII at the Volterra conference on alcohol and stress, May 2008

Abstract 

This report summarizes the proceedings of the symposium VII on the role of neuroactive steroids in stress/alcohol interactions. The production of GABAergic neuroactive steroids, including (3α,5α)-3-hydroxypregnan-20-one and (3α,5α)-3,21-dihydroxypregnan-20-one is a consequence of both acute stress and acute ethanol exposure. Acute, but not chronic ethanol administration elevates brain levels of these steroids and enhances GABA_A receptor activity. Neuroactive steroids modulate acute anticonvulsant effects, sedation, spatial memory impairment, anxiolytic-like, antidepressant-like, and reinforcing properties of ethanol in rodents. Furthermore, these steroids participate in the homeostatic regulation of the hypothalamic–pituitary–adrenal axis. Therefore, it is not surprising that neuroactive steroids are involved in ethanol/stress interactions. Nevertheless, the interactions are complex and not well understood. This symposium addressed the role of neuroactive steroids in both stress and alcohol responses and their interactions. Professor Giovanni Biggio of the University of Cagliari, Italy presented the effects of juvenile isolation stress on neuroactive steroids, GABA_A receptor expression, and ethanol sensitivity. Professor Howard Becker of the Medical University of South Carolina, USA presented evidence for neuroactive steroid involvement in ethanol dependence and drinking behavior. Professor Patrizia Porcu of the University of North Carolina, USA described a potential neuroactive steroid biomarker that may predict heavy drinking in monkeys and mice. These presentations provide a framework for new theories on the nature of ethanol/stress interactions that may be amenable to therapeutic interventions.

Keywords: Neuroactive steroids, GABA_A receptors, Social isolation, C57BL/6J mice, DBA/2J mice, HPA axis

Abbreviations: GABA, γ-aminobutyric acid, 3α,5α-THP, (3α,5α)-3-hydroxypregnan-20-one, 3α,5α-THDOC, (3α,5α)-3,21-dihydroxypregnan-20-one, HPA, hypothalamic–pituitary–adrenal, CNS, central nervous system, CRF, corticotropin releasing factor, ACTH, adrenocorticotropic hormone in, mIPSCs, miniature inhibitory postsynaptic currents, BAL, blood alcohol levels