deficits in BDNF-Arc signaling and dendritic spine density in the amygdala upon withdrawal from chronic ethanol exposure (You et al., 2014). Furthermore, HDAC inhibition was able to reverse the development of rapid tolerance to the anxiolytic effects of ethanol and increase histone acetylation and NPY levels in the amygdala (Sakharkar, Zhang, Tang, Shi, & Pandey, 2012). The popular genetic model of alcohol consumption, alcohol-preferring (P) and -nonpreferring (NP) have been used to successfully characterize alcohol drinking behaviors and their comorbidity with anxiety-like behaviors (Pandey et al., 2005; Prakash, Zhang, & Pandey, 2008; Zhang et al., 2010). It was shown that innate deficits in the BDNF-Arc pathway, by regulating dendritic spine density, was operative in regulating the anxiety-like and excessive ethanol-drinking behaviors of P rats as compared to NP rats (Moonat et al., 2011) (Figure 2). The epigenetic mechanisms of these deficits were further investigated, and it was found that innate HDAC2 levels were higher in the amygdala of P as 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.
