High-throughput sequencing has a low background signal, facilitates identification and absolute quantification of low-abundance and novel transcripts (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). We used next-generation sequencing of mRNAs purified from the NAc to obtain a more complete picture of the molecular response to chronic cocaine exposure and withdrawal. Bioinformatic analysis of cocaine-regulated transcripts revealed substantial involvement of the Wnt/cadherin and heterotrimeric G-protein signaling pathways. Evaluation of the synthetic enzymes, transporters, and receptors involved in catecholaminergic, glutamatergic, GABAergic, cholinergic, and lipid signaling identified complex responses unique to cocaine and withdrawal.
