Using a chronic intermittent ethanol exposure model, a robust H3K9 hyperacetylation was seen in the AMG and cortical areas of rats, which displayed motivation to self-administer ethanol after a 6-h withdrawal period, compared with non-dependent rats (133). Treatment with the HDACi NaB or MS-275 (i.p. or i.c.v.) was able to counteract the effects of alcohol in dependent rats but not in non-dependent rats. Treatment with NaB, when administrated prior to ethanol self-administration, was also able to reverse H3K9 hyperacetylation and counteract excessive alcohol intake and relapse in alcohol-dependent rats. In order to identify brain region-specific regulatory molecular (epigenetic) signatures potentially involved in adaptive processes that lead to alcohol tolerance and dependence, Smith and colleagues (134) recently examined brain regional expression network responses to acute (0–8 h) and late (72 h to 7 days) withdrawal from chronic intermittent ethanol exposure in mice. Remarkably, the authors showed that neuroinflammatory responsive genes can be seen across all brain regions at 0–8 h after the beginning of alcohol withdrawal, while sustained over-representation for subset groups of genes related to neurodevelopment and synaptic plasticity (such
