Brain pattern of histone H3 phosphorylation after acute amphetamine administration: Its relationship to brain c-fos induction is strongly dependent on the particular brain area

Recent evidence strongly suggests a critical role of chromatin remodelling in the acute and chronic effects of addictive drugs. We reasoned that Immunohistochemical detection of certain histone modifications may be a more specific tool than induction of immediate early genes (i.e. c-fos) to detect brain areas and neurons that are critical for the action of addictive drugs. Thus, in the present work we studied in adult male rats the effects of a high dose of amphetamine on brain pattern of histone H3 phosphorylation in serine 10 (pH3S10) and c-fos expression. We firstly observed that amphetamine-induced an increase in the number of pH3S10 positive neurons in a restricted number of brain areas, with maximum levels at 30 min after the drug administration that declined at 90 min in most areas. In a second experiment we studied colocalization of pH3S10 immunoreactivity (pH3S10-IR) and c-fos expression. Amphetamine increased c-fos expression in medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens (Acb), major Island of Calleja (ICjM), central amygdala (CeA), bed nucleus of stria terminalis lateral dorsal (BSTld) and paraventricular nucleus of the hypothalamus (PVN). Whereas no evidence for increase in pH3S10 positive neurons was found in the mPFC and the PVN, in the striatum and the Acb basically all pH3S10 positive neurons showed colocalization with c-fos. In ICjM, CeA and BSTld a notable degree of colocalization was found, but an important number of neurons expressing c-fos were negative for pH3S10. The present results give support to the hypothesis that amphetamine-induced pH3S10-IR showed a more restricted pattern than brain c-fos induction, being this difference strongly dependent on the particular brain area studied. It is likely that those nuclei and neurons showing pH3S10-IR are more specifically associated to important effects of the drug, including neural plasticity.This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’.

► Amphetamine increased phosphorylation of histone H3 (pH3S10) in several brain areas.
► Enhanced pH3S10 after amphetamine is a relative fast and transient phenomenon.
► Pattern of pH3S10 caused by amphetamine is more restricted than that of c-fos.
► pH3S10 may identify areas and neurons important for the effects of amphetamine.