2011; Vogel-Ciernia and Wood, 2014). For example, alcohol dependence is mechanistically associated with altered chromatin remodeling that leads to alcohol withdrawal induced anxiety, a phenotype arising in part from altered synaptic plasticity in limbic regions of the brain (Krishnan et al., 2014). This chromatin remodeling causes a reduction in expression of NPY in the amygdala which fits with enhanced anxiety during alcohol withdrawal (Pandey et al., 2008). In addition, the SWI/SWF chromatin remodeling complex is required in adult neurons of C.elegans for acute alcohol tolerance and genetic variation in a member of this complex is associated with alcohol dependence in humans (Mathies et al., 2015). Interestingly, a recent study demonstrated that the sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope, suppressing the expression of monoamine oxide B (MAOB) in the nucleus accumbens (Tsai et al., 2015). This is a remarkably novel mechanism of action of cocaine mediated by transcriptional mechanisms associated with the sigma-1 receptor. In animal models, sigma-1 receptor antagonists decrease alcohol intake and reinforcement learning (Sabino et al., 2009a) and reduce excessive alcohol consumption in alcohol preferring rat selectively bred lines (Sabino et al., 2009b). Therefore, the sigma-1 receptor may perform a
