Chunk #21 — 3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain
(Alaux-Cantin et al., 2013; Sakharkar et al., 2014). Treatment with the HDAC inhibitor sodium butyrate blocked both the acquisition and the expression of ethanol-induced behavioral sensitization in mice (Legastelois et al., 2013). Furthermore, systemic treatment of HDAC class I and II inhibitors, TSA and SAHA (suberanilohydroxamic acid), and the more selective MS-275 (a histone deacetylase inhibitor), decreased binge-like ethanol consumption in mice (Warnault et al., 2013). Intracerebral injection of MS-275 also increased acetylation of HDAC4 in the nucleus accumbens and striatum of dependent rats, which reduced ethanol self-administration, suggesting that it produced a direct central nervous system (CNS) effect (Jeanblanc et al., 2015). HDAC inhibitors can also reverse ethanol-induced changes in neuronal transmission; for example, treatment with TSA or SAHA reversed GABA hyposensitivity of ventral tegmental area dopaminergic neurons in mice during withdrawal (Arora et al., 2013). In a clinical study, the HDAC inhibitor, valproate, attenuated withdrawal symptoms and relapse in human alcoholics (Longo et al., 2002; Myrick et al., 2000). These data provide evidence that certain HDAC inhibitors may have therapeutic efficacy by reversing alcohol-induced epigenetic modifications and normalizing aberrant gene expression changes after chronic alcohol exposure.
