Understanding the role played by HDACs in alcoholism and other drugs of abuse disorders is critical to understanding the etiology of addictive behaviors and at the same time providing a therapeutic avenue to treat these conditions. In a series of recent studies using preclinical models, Pandey’s laboratory have extensively investigated the HDAC-mediated chromatin remodeling pathways in the amygdala that play a role in the comorbidity of anxiety and alcohol-use disorders using both unselected and selected alcohol-preferring rat models. Inhibition of HDAC using Trichostatin A (TSA) was found to alleviate the symptoms of anxiety and reverse deficits in histone acetylation, NPY expression, and BDNF-Arc pathway in the amygdala upon withdrawal from chronic ethanol in adult male Sprague Dawley rats (Pandey, Ugale, et al., 2008; You, Zhang, Sakharkar, Teppen, & Pandey, 2014) (Figure 2). In addition, TSA treatment was able to normalize 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
