Environmental stressors and alcoholism development: Focus on molecular targets and their epigenetic regulation

Alcohol exposure and stressful events in life can induce long-lasting changes in physiology, behavior and gene expression patterns, eventually facilitating the development of psychiatric diseases like alcohol use disorders (AUD). Epigenetic mechanisms have been recently proposed to play a role in the cellular actions of alcohol via chromatin remodeling. Here we discuss interactions between stress and the pharmacological effects of alcohol, including the possibility that early exposure to, or withdrawal of, alcohol might induce stressful effects of their own. A specific aim is to describe novel molecular mechanisms by which stress, alcohol or their combined presentation impact on the epigenome. A key question is why only a fraction of the population progresses from regular, non-problematic, alcohol use to AUD, despite suffering from similar alcohol exposure. It is important to analyze how environmental factors, most notably stress, interact with the epigenetic machinery to increase vulnerability for AUD. The knowledge derived from this endeavor will be critical for the development of preventive strategies and new, drug- or gene-based, therapies.