Cdk5 genes and the wellcharacterized increase in the expression of their associated proteins after chronic cocaine exposure.58-62 Further, viral-mediated overexpression of HDACs in striatal tissues decreased,44,57 whereas genetic or pharmacological knockout of striatal HDACs increased sensitivity to the rewarding effects of cocaine, as measured in a place conditioning procedure.44,57 These data demonstrate that cocaine-induced modifications in histone acetylation state play a critical role in regulating the effects of cocaine in mice. More recently, histone methylation and other chromatin modifications, and even DNA methylation status, have all been implicated in regulating cocaine-induced changes in gene expression in brain reward systems.3,63-67
