the fact that these drugs produce mutual cross-tolerance. Among the 144 shared candidates discovered, the top gene clusters based on gene ontology belonged to the categories of transcriptional regulation, ion channels and synaptic plasticity genes (Ghezzi et al., 2013). Next-generation sequencing approaches have been used to determine global methylation levels in human post-mortem brains of alcoholics. Alcoholic brain tissue display an overall decrease in methylation, especially at long-terminal repeat containing endogenous retroviruses which corresponded to their activation as well as upregulation of GC rich genes and associated histone H3K4 tri-methylation (Ponomarev et al., 2012). These epigenetic alterations may contribute to the widespread changes in gene expression and in the global transcriptome following chronic ethanol exposure. These methodologies offer a novel way to identify and characterize epigenetic networks that are unique to a single drug and also that are shared following exposure to different drugs sharing similar phenotypes and/or affecting the same neuroanatomical circuits.