Chunk #22 — 3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain
The findings outlined above suggest that epigenetic alterations within addiction-related brain circuits in the frontal cortex and hippocampus could perturb the regulation of cognitive and emotional processes, resulting in an overvaluing of drug reinforcers at the expense of undervaluing natural rewards (Koob and Volkow, 2010, 2016; Volkow et al., 2016). Moreover, changes in epigenetic regulation in the hippocampus could produce widespread gene expression changes that lead to aberrant neuroadaptations in conditioned learning and declarative memory (White, 1996). Gene expression alterations in the extended amygdala circuit, including the basolateral and central nucleus of the amygdala, could contribute to anxiety/aversive-like effects of acute withdrawal and increased drug intake associated with dependence (Koob and Volkow, 2010; Volkow et al., 2016). Thus, alcohol-induced epigenetic regulation has the potential to impact different stages of the addiction cycle (Fig. 1). Moreover, some HDAC inhibitors, such as SAHA, are already approved for treatment of primary cutaneous T-cell lymphoma and other types of cancer while other HDAC inhibitors are in clinical trials for neuropsychiatric disorders (Falkenberg and Johnstone, 2014). Therefore, HDAC inhibitors represent a potential class of drug that could be repurposed for the treatment of AUD.
