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.