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 is associated with chromatin de-condensation and repeated ethanol exposure gradually leads to a persistent drinking phenotype and upon withdrawal, causes chromatin condensation and the phenotypes of increased anxiety, which in-turn promote increased consumption. This phenomenon is dependent on HDAC activity and, as long as ethanol is present in the bloodstream, HDAC activity is inhibited. However upon withdrawal, a rebound increase in HDAC activity and chromatin condensation occurs (Figure 3). Administration of HDAC inhibitors at the appropriate time point alleviates the negative dysphoric effects seen upon withdrawal which could prove to be an effective way to reverse the process of alcoholism (Pandey, Ugale, et al., 2008; Moonat et al., 2013; Sakharkar, Zhang, et al., 2014; You et al., 2014). In a similar fashion, positive euphoric effects of alcohol can be modulated by epigenetic changes in the reward circuitry and HDAC inhibitors can reverse HDAC-induced adaptational mechanisms during alcohol withdrawal (Arora et al., 2013). Thus by affecting both the positive and negative
