Prolonged Access to Cocaine Results in Distinct Epigenetic Changes in the Prefrontal Cortex (LB622)

DNA methylation is a key determinant of gene expression and is implicated in neuroplasticity relevant to addiction. Here, we examine DNA methylation and mRNA expression for two genes, Homer2 and NPAS4, within the dorsal medial prefrontal cortex (dmPFC) following saline, short-access (1h), or prolonged-access (6h), to cocaine during self-administration. As reported previously, only 6h rats exhibited escalated cocaine intake across sessions. Initial MeDIP-CHIP analyses of dmPFC tissue by ChIPMonk software revealed dramatic and extremely gene-specific changes in DNA methylation/demethylation within promoter regions and flanking the transcription start site (TSS). The Homer2 and NPAS4 promoters showed active changes in DNA methylation following 6h and 1h cocaine self-administration compared to saline. A follow-up analysis, via sodium bisulphite conversion followed by mass spectrophotometry interrogating a 1000bp sequence of the Homer2 promoter, confirmed increased methylation of CpG7 in the 6h rats, which con...