There have been numerous studies of cocaine regulation of gene expression in the NAc and other brain regions by gene expression arrays. This research has revealed large numbers of transcripts that are altered in response to cocaine administration. The ChIP-chip studies reported here enable the coordinated use of both approaches to identify a smaller set of genes in which the field can place greater confidence as being bona fide targets of cocaine and the key transcription factors which mediate cocaine’s effects. Moreover, this work begins to describe the specific mechanisms underlying these cocaine-induced transcriptional changes and reveals fundamentally new insight into the genome-wide patterns of chromatin regulation by cocaine in the NAc. Together, this new insight has led to the identification of a novel family of genes involved in cocaine action in the NAc, the sirtuins, which, as we have shown, play an essential role in addiction-like behavior.
