Phosphorylation of histones is associated with transcriptional activation, DNA repair and cell-cycle dynamics and is mediated by protein kinases and removed by phosphatases (Banerjee & Chakravarti, 2011; Bannister & Kouzarides, 2011). Histone H3 phosphorylation has been shown to regulate important neuronal pathways. For example, histone H3 phosphorylation at serine 10 has been implicated in a contextual fear-conditioning model in the hippocampus (Chwang, O’Riordan, Levenson, & Sweatt, 2006). The protein kinase ribosomal S6 kinase 2 (RSK2) has been shown to phosphorylate histone H3 and CREB and, in the presence of CBP, mediate a combined acetylation-phosphorylation event that regulates chromatin remodeling (Merienne, Pannetier, Harel-Bellan, & Sassone-Corsi, 2001). The psychostimulant drugs, amphetamines and cocaine, as well as morphine have been found to increase phosphorylation of serine 10 of histone H3 which further results in sequestration of dopamine- and cyclic-AMP regulated phosphoprotein 32 (DARPP-32) in the nucleus which inhibits protein phosphatase-1, thereby promoting phosphorylation. Blocking this phosphorylation event at serine 10 on H3 was able to diminish the behavioral responses to both cocaine and morphine and blocked conditioned place preference for cocaine (Stipanovich et
