dendritic spine densities in the central and medial AMG nuclei, withdrawal from prolonged ethanol exposure or binge ethanol consumption potently inhibited BDNF and Arc expression and reduced dendritic arborization in these nuclei and other regions, leading to increased anxiety-like and drinking behaviors (66, 129, 130). Importantly, these long-lasting adaptive changes associated with alcohol dependence were reversed upon treatment with the HDACi TSA (61, 128–130). In another study by Moonat and colleagues (61) examining the role of HDAC2 in the development of alcohol dependence, investigators found lower baseline BDNF protein levels in the AMG (and also the bed nucleus of stria terminalis) of alcohol-preferring rats, a well-established model used to study the genetic predisposition to alcoholism (131), relative to the low-drinking NP rats. In addition, innate HDAC2 overexpression and decreased H3K9 acetylation in the central nucleus of alcohol-preferring rats correlated with low levels of BDNF, Arc, and NPY and was accompanied with high levels of anxiety-like and alcohol-drinking behaviors. These HDAC2-associated molecular and behavioral deficits were rescued via specific knockdown of HDAC2 expression either by direct infusion of small interfering RNA (siRNA) against HDAC2 into the central AMG nucleus (61, 66) or by TSA treatment (127, 130, 132). Collectively, these observations
