methylation repressive mark as well as a downregulation of a set of histone methyltransferases (HMT) (155, 156). These changes mostly occurred after ethanol removal and contributed to the development of physical dependence on alcohol through an adaptive long-lasting upregulation of the NMDA receptor 2B (NR2B) gene expression (155). Moreover, systemic treatment with TSA during ethanol exposure increased H3K9 acetylation at the NR2B promoter in PFC neurons and potentiated voluntary ethanol consumption (157). Together, these data suggest that persistent upregulation of the NR2B-containing NMDA receptors through deregulation of the balance between histone H3K9 acetylation and methylation states in the PFC may act as a potentially important contributor to the development of alcohol dependence.
