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 drug‑induced behavior and neuroplasticity impairment. Brahma/SWI2‑related gene‑1 (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 self‑administration. The present study established a Sprague‑Dawley rat model of heroin self‑administration under a fixed‑ratio‑1 paradigm. Chromatin immunoprecipitation followed by reverse transcription‑quantitative PCR (RT‑qPCR) was used to detect the accumulation of H3K9ac on BRG1 in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) following heroin self‑administration. The relative expression levels of BRG1 were analyzed by RT‑qPCR. H3K9ac at the promoter region of BRG1 was significantly elevated (P=0.002), and the expression of BRG1 in the mPFC increased 1.47‑fold in the heroin self‑administration 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 1.38‑fold in the heroin self‑administering 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 H3K9ac‑mediated regulation in the mPFC after heroin self‑administration; and this may function through epigenetically modulating the activation of neuroplasticity‑associated genes. This association may provide a novel therapeutic target for the treatment of heroin addiction.

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