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Extended Cocaine Access Results in a Distinct Epigenetic Alterations to the Homer2 Gene in the Dorsal Medial Prefrontal Cortex
Author(s) -
Ploense Kyle,
Carr Amanda,
BakerAndresen Danay,
Li Xiang,
Sun Yi,
Bredy Timothy,
Kippin Tod
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.705.11
Subject(s) - epigenetics , dna methylation , messenger rna , gene expression , prefrontal cortex , methylation , biology , gene , transcription factor , microbiology and biotechnology , endocrinology , genetics , neuroscience , cognition
DNA methylation is a key determinant of gene expression and is implicated in neuroplasticity relevant to addiction. Here, we examine DNA methylation, hydroxymethylation, binding of the transcription factor p300, and mRNA expression within the dorsal medial prefrontal cortex (dmPFC) following limited cocaine self‐administration (1h), prolonged cocaine self‐administration (6h), and saline self‐administration (1h). Rats were fitted with IV catheters and allowed to lever press for saline or cocaine (0.25mg/kg/infusion) in the different access conditions for 20 days. 6h rats exhibited escalation in cocaine intake over the course of training, and had a distinct epigenetic profile and mRNA expression pattern for the Homer2 gene. qPCR analyses revealed an increase in Homer2 mRNA levels in the dmPFC for 6h rats only. The changes in mRNA were accompanied by lower DNA methylation, increased DNA hydroxymethylation, and decreased p300 binding in the Homer2 promoter; these 3 epi‐marks in the promoter allotted for an open transcriptional state in the 6h rats that was not present in the 1h or saline rats that allowed for increased Homer2 mRNA transcription.