Although the role of lncRNAs in alcohol dependence is still unclear, they are known to 1) regulate epigenetic factors and gene expression (Khalil et al., 2009; Lee, 2012; Wang et al., 2011), 2) act as endogenous competitors (Cesana et al., 2011), 3) regulate alternative splicing events (Barry et al., 2014; Massone et al., 2011; Tripathi et al., 2010), and 4) alter synaptic plasticity (Bond et al., 2009), all of which are important mechanisms in AUD. Interestingly, there may be overlap in drug-responsive lncRNAs that are altered by alcohol dependence and other substance abuse disorders. For example, nuclear-enriched abundant transcript 2 (NEAT2), a lncRNA important in synaptogenesis (Bernard et al., 2010), was up-regulated in human alcoholic brain (Kryger et al., 2012). NEAT2, and other related lncRNAs, were also up-regulated in the nucleus accumbens of heroin (e.g., NEAT1, MIAT, and MEG3) and cocaine abusers (e.g., MIAT, MEG3, and EMX2OS) (Albertson et al., 2004; Michelhaugh et al., 2011). Thus, different types of substance abuse/dependence may produce overlapping changes in related lncRNAs. Given that lncRNAs fulfill diverse roles in the CNS, even small changes in lncRNA expression could significantly impact patterns of chronic alcohol consumption (Fig. 1).
