Single-gene, proteomic, and microarray analyses demonstrated that cocaine produces widespread, multi-faceted responses in the NAc (McClung and Nestler, 2008; Eipper-Mains et al., 2011). Next-generation sequencing identified pathways not previously thought to play any role in addiction and facilitated systematic cataloging of changes in all components of known signaling pathways. With greater sequencing depth, changes in editing, splicing, imprinting and allele-specific expression can be quantified (Mortazavi et al., 2008; Wang et al., 2008a; Wang et al., 2008b; Wahlstedt et al., 2009; Wang et al., 2009; Metzker, 2010; Eipper-Mains et al., 2011). In situ hybridization and immunostaining will be required to localize changes in gene expression to specific cell types in the core and shell regions of the NAc. Components of the Wnt, cadherin, and heterotrimeric G-protein signaling pathways were over-represented among cocaine-responsive transcripts; cross-talk between these signaling cascades is extensive (Force et al., 2007).
