Histone 3 lysine 9 acetylation of BRG1 in the medial prefrontal cortex is associated with heroin self‑administration in rats

Heroin addiction is a chronic relapsing brain disorder with negative social consequences. Histone acetylation serves a role in druginduced behavior and neuroplasticity impairment. Brahma/SWI2related gene1 (BRG1) participates in cerebellar development, embryogenesis and transcriptional regulation of neuronal genes concurrent with histone modifications. However, little is known about the relationship between histone H3 lysine 9 acetylation (H3K9ac) and BRG1 in response to heroin. The present study aimed to assess the contribution of histone 3 lysine 9 acetylation of BRG1 to heroin selfadministration. The present study established a SpragueDawley rat model of heroin selfadministration under a fixedratio1 paradigm. Chromatin immunoprecipitation followed by reverse transcriptionquantitative PCR (RTqPCR) was used to detect the accumulation of H3K9ac on BRG1 in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) following heroin selfadministration. The relative expression levels of BRG1 were analyzed by RTqPCR. H3K9ac at the promoter region of BRG1 was significantly elevated (P=0.002), and the expression of BRG1 in the mPFC increased 1.47fold in the heroin selfadministration group compared with the control group. No significant difference in H3K9ac at the BRG1 locus was observed in the NAc (P=0.323), with the expression of BRG1 decreasing 1.38fold in the heroin selfadministering rats compared with the control group. H3K9ac is associated with transcriptional activation, and the increased BRG1 expression suggested an essential and novel role for BRG1 and its H3K9acmediated regulation in the mPFC after heroin selfadministration; and this may function through epigenetically modulating the activation of neuroplasticityassociated genes. This association may provide a novel therapeutic target for the treatment of heroin addiction.