regulate amygdaloid chromatin assembly, and alter the expression of genes implicated in alcohol preference, tolerance and dependence. HDAC2 specific inhibition in the amygdala might be a therapeutic option to reduce the dysphoric symptoms of alcohol-use that are comorbid with anxiety and characterize the negative affective state of alcoholism (Moonat et al., 2013). Similarly, others have also shown that ethanol intake reduced histone H4 acetylation in the nucleus accumbens (NAc) in two rodent models and that HDAC inhibitor treatment (using both TSA and the FDA-approved HDAC inhibitor SAHA) reduced excessive ethanol drinking in mice and ethanol-seeking behaviors in rats (Warnault, Darcq, Levine, Barak, & Ron, 2013). In an ethanol-induced behavioral sensitization model, ethanol was shown to increase H4 acetylation in the NAc, which corresponded to a decrease in HDAC activity in the striatum (Botia, Legastelois, Alaux-Cantin, & Naassila, 2012). This was attenuated by treatment with the HDAC inhibitor, sodium butyrate, and associated with increased BDNF expression in the striatum (Legastelois, Botia, & Naassila, 2013). Opioid signaling pathways in the amygdala have also been identified as an epigenetic target of ethanol. Alcohol dependence has been shown to be associated with abnormal regulation of the Dynorphin/κ-opioid system with increased consumption linked to activation
