Ethanol’s effects on histone H3 phosphorylation at serine 10 (H3ser10phos) and concurrent H3 phosphoacetylation are of particular interest as their rapid elevation is critical for leaning/memory-associated induction of immediate-early genes (e.g., c-fos and egr-1) (141–143), an effect shown to mediate adaptive responses to psychology stressful events such as forced swimming or novelty stress paradigm exposure (142–145). In rats, acute ethanol dose dependently alters the number of H3ser10phos in the dentate granular cells of the HPC, and these changes are paralleled by changes in c-fos protein expression (146). The same group has shown that, in ethanol-dependent rats, both H3ser10phos and c-fos levels are reduced in dentate granule cells during excessive alcohol intake, while opposite effects are evident at withdrawal peak in the HPC. Elevation of H3ser10phos and histone H3 phosphoacetylation is achieved through a direct interaction of the GR with [mitogen- and stress-activated protein kinase 1 (MSK1)] and ETS-domain protein Elk-1 that are downstream of the ERK/MAPK signaling cascade (143, 145, 147, 148). Conversely, nuclear type 1 protein phosphatase (PP1), a nuclear protein Ser/Thr phosphatase that acts as a universal negative
