This review summarizes recent advances in our comprehension of endocrine, epigenetic, and transcriptional changes that serve as determining factors in controlling alcohol-associated changes in the expression of gene networks and behavior and play a central role in the regulation of alcohol dependence, withdrawal, and relapse (Figure 1). Most of the studies conducted thus far focused mainly on epigenetic and transcriptional regulation of adaptive responses to acute and chronic alcohol that occur within a single brain region (mostly the AMG). This review highlights new evidence from clinical and preclinical studies on how long-term adaptations arising from disruption of the fine coordination of highly interconnected brain structures within a circuit, including, but not limited to, the PFC, the HPC, and the AMG, may contribute to excessive alcohol consumption and alcohol dependence as well as behavior impairments. The findings reviewed in this article support the view that brain region- and cell type-specific histone acetylation modification (both in terms of global/genome-wide changes as well as promoter-specific changes) is a key mechanism underlying anxiety-like and alcohol-drinking behaviors. Thus, treatments designed to counteract alcohol-associated epigenetic changes may be promising targets for novel medications in the treatment of alcoholism.
