This review briefly summarized different epigenetic pathways that contribute to the phenotypes observed after alcohol use leading to continued use and dependence, which ultimately predisposes to alcoholism. We also provided examples of the epigenetic basis of other brain diseases in order to emphasize the importance of epigenetic regulation in brain disorders. Chronic ethanol changes the epigenome, thereby regulating the transcriptome, which alters neuroplasticity in specific neuroanatomical substrates, and eventually, leading to the phenotypic changes seen in alcoholism. This plasticity leads to the negative dysphoric states, such as anxiety, that are usually comorbid with alcoholism and are alleviated by consumption of ethanol or HDAC inhibition in the amygdala (Pandey, Ugale, et al., 2008; Moonat et al., 2013; Sakharkar, Zhang, et al., 2014). Although the DNA methylation pathways and mechanisms that control this transition are unclear, data is emerging that histone acetylation/de-acetylation pathway proteins that are responsible for covalent modifications to histones, play an important part in the central nucleus of amygdala in the co-morbidity of anxiety and alcohol use disorders. We have shown that the anxiolysis produced by acute ethanol exposure
