Histone deacetylase inhibition decreases preference without affecting aversion for nicotine.

摘要: Epigenetic mechanisms have recently been shown to be involved in the long-term effects of drugs abuse. A well described epigenetic mechanism modulating transcriptional activity consists binding DNA methyl-CpG proteins, such as MeCP2, recruiting histone deacetylases (HDACs). Nicotine causes changes brain, but little is known concerning nicotine-preference. Using a nicotine-conditioned place preference protocol, we demonstrate here that deacetylase inhibitor phenylbutyrate was able dramatically reduce for nicotine, without altering aversive properties drug. We measured immunohistochemically acetylation lysine-9 H3, and expression phosphorylated cAMP-response element-binding protein, HDAC2 methyl-CpG-binding protein 2 striatum prefrontal cortex rats displaying nicotine-preference or aversion treated with phenylbutyrate. show that, at dose administered, effective inhibiting HDAC activity. The data suggest participates establishment conditioned preference, not reduction response Moreover, striatal mirrored behavioral inhibitor, suggesting promoting synaptic plasticity underlying nicotine.