Acute exposure to cocaine or amphetamine, for example, which are known to rapidly induce the immediate early genes c-fos and fosb in the NAc, increases histone H4 acetylation and phospho-acetylation of H3 on their proximal gene promoters (Figure 1) [53, 54]. Time course analysis after cocaine revealed that this modification occurs within 30 minutes and disappears by 3 hours, consistent with the induction kinetics of these immediate early genes [53]. At least for fosb, this increase in histone acetylation is dependent on the HAT, CBP [34]. While the specific HAT responsible for acetylating c-fos after cocaine remains to be identified, there is evidence that the downstream mitogen activated protein kinase, MSK1 is responsible for cocaine-induced increases in H3S10 phosphorylation (Figure 1) [55]. A recent study has also implicated the nuclear accumulation of DARPP32, a protein phosphatase 1 (PP1) inhibitor, in mediating cocaine induction of H3S10 phosphorylation [56]. Interestingly, despite several control gene promoters where acute cocaine does not affect histone acetylation (β-tubulin, tyrosine hydroxylase, histone H4) [53], acute cocaine does increase global levels of histone H4 acetylation and histone H3
