Of all the genes in the NAc that show markers of activation or repression after chronic cocaine, roughly 14% exhibit altered levels of ΔFosB binding and roughly 16% exhibit altered levels of phospho-CREB binding (Fig. 2A; Supplemental Fig. S2; Supplemental Tables S8, S11). This is interesting in that our previous DNA expression array study found that similar fractions of genes regulated in the NAc after 5 days of cocaine were also regulated upon ΔFosB overexpression or CREB overexpression, respectively (McClung and Nestler, 2003). The number of cocaine-regulated genes influenced by ΔFosB increased to >25%, whereas that for CREB decreased to 5%, after 4 weeks of cocaine administration, which illustrates the importance of performing genome-wide ChIP-chip and gene expression studies after longer periods of cocaine exposure and different time points of cocaine withdrawal.
