and/or transcription factor binding. These are particularly interesting examples given the potent influence of HDAC4 (Kumar et al., 2005) and of MEF2 (Pulipparacharuvil et al., 2008) in the NAc on cocaine responses, and may illustrate a new layer of regulation not previously appreciated. Similar disconnects between gene activity and gene or protein expression have been observed during cocaine withdrawal (Self et al., 2004). Bdnf is a good example where hyperacetylation of its promoter (Kumar et al., 2005) does not correlate with an immediate increase in steady state BDNF expression, however, during cocaine withdrawal, levels of BDNF protein become significantly elevated (Grimm et al., 2003). Similarly, gene expression arrays found increased MEF2D expression in the NAc after extinction from cocaine self-administration (personal communication, D.W. Self). Thus, histone acetylation at certain genes may represent a priming mechanism to facilitate subsequent gene induction. Taken together, our study corroborates numerous established molecular targets of cocaine action in the NAc, and demonstrates the power of ChIP-chip assays to uncover in a comprehensive manner the genomic targets through which cocaine induces neural and behavioral plasticity in this critical brain reward region. A still further advance would be to determine whether these various cocaine-induced changes in NAc
