Repeated use of addictive drugs such as cocaine causes long-lasting changes in the brain’s reward circuitry, a key component of which is the nucleus accumbens (NAc). Accordingly, a major goal in the field has been to uncover the molecular mechanisms underlying addiction-associated neuroadaptations in this brain region. It has been hypothesized that one such mechanism is the regulation of gene expression (Hyman et al., 2006), and there have been numerous studies that have documented altered expression of genes, through candidate gene approaches or through gene expression arrays, in the NAc (Freeman et al., 2001; McClung and Nestler, 2003; Yao et al., 2004). As well, several transcription factors have been shown to be altered in the NAc after chronic cocaine exposure, including ΔFosB (a Fos family protein) (Hiroi et al., 1997; Nestler, 2008) and CREB (cAMP response element binding protein) (Carlezon et al., 2005), which have both been related directly to the behavioral abnormalities that characterize an addicted state.
