The discovery of new mechanisms of ethanol actions on GABAergic transmission over the past 10 years opens new opportunities to intervene in the effects of ethanol on different aspects of brain function. It is now possible to inhibit effects of ethanol by blockade of α4-GABAA receptors or by inhibition of neuroactive steroid synthesis. The blockade of ethanol actions may prevent ethanol-induced toxicity and/or facilitate increased consumption due to the loss of ethanol sensitivity. Likewise, it is also possible to enhance ethanol sensitivity by targeting α4-GABAA receptors with selective agonists or promoting neuroactive steroid synthesis. While there are many advances in the molecular realm, it remains unclear whether it is advantageous or disadvantageous to manipulate ethanol actions in humans. Future studies are clearly needed to elucidate the therapeutic relevance of the advances of the last 10 years.
