Expression of the D3 dopamine receptor (Drd3) increased in response to Cocaine and remained elevated after Withdrawal (cluster i); in contrast, D2 dopamine receptor (Drd2) expression increased only after Withdrawal. An increase in D3 receptor expression was observed in the NAc of cocaine overdose victims (Mash and Staley, 1999) and in rats 45 days after cocaine self-administration ceased (Conrad et al., 2010). Recent work suggests that dopamine receptor dysregulation, mediated by decreased D2 and increased D3 receptor expression, contributes to increased cocaine-seeking behavior after prolonged withdrawal (Conrad et al., 2010). Alterations in serotonin signaling are also recognized as important in drug addiction (Dreyer, 2010), and we observed cocaine-responsive changes in gene expression across many of the serotonin receptors.
