compared with NP rats, which corresponded to lower H3K9 acetylation globally and specifically at the promoters of BDNF and Arc genes corresponding to decreased expression of BDNF and Arc. These ultimately resulted in lower dendritic spine density in the amygdala. These alterations were ameliorated by infusion of HDAC2 siRNA into the central nucleus of amygdala (CeA), resulting in anxiolytic effects and reducing voluntary ethanol intake (Moonat, Sakharkar, Zhang, Tang, & Pandey, 2013) (Figure 2). Similarly, TSA treatment reduced the innately anxiety-like behaviors and ethanol intake in P rats, via inhibition of HDAC activity due to a reduction in HDAC2 protein levels in the CeA and medial nucleus of amygdala (MeA). TSA treatment also corrected the deficits in H3K9 acetylation levels globally and specifically at the NPY gene promoter, which correlated with increased NPY expression in the CeA and MeA of P rats (Sakharkar, Zhang, et al., 2014). Taken together, these data suggest that epigenetic modifications involving HDACs (namely HDAC2) may 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
