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The effect of cocaine cue re‐exposure after prolonged cocaine self‐administration and forced abstinence on DNA methylation and mRNA expression in the rat dmPFC
Author(s) -
Ploense Kyle L.,
Vieira Philip,
Carr Amanda,
Purpura Mari,
Kippin Tod
Publication year - 2018
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.2018.32.1_supplement.782.13
Subject(s) - abstinence , dna methylation , epigenetics , addiction , context (archaeology) , methylation , biology , gene expression , gene , pharmacology , psychology , genetics , neuroscience , psychiatry , paleontology
Cocaine addiction is a chronic relapsing disorder whereby cocaine craving in response to drug related cues persists, and even intensifies through protracted drug‐free abstinence periods. Studies employing animal models observe cocaine‐seeking patterns that are similar to human addicts. Additionally, there are long term changes in neuron structure, receptor function, and neurotransmission associated with abstinence from cocaine in humans and animals. DNA methylation is an epigenetic modification to the DNA structure that mediates mRNA expression to confer different cell types, but has recently been implicated in learning and memory mechanisms. The long‐term control that DNA methylation has over gene expression in animals makes it a prime candidate for controlling gene expression over the course of abstinence in animals with previous drug experience. To test this, I trained rats to self‐administer either saline (1 h per day) or cocaine (6 h per day) for 15 days, then exposed them to 60 days of forced abstinence. After abstinence half of the rats were put back in self‐administration chambers and re‐exposed to cues for 2 h, while the other half were left in their home cages. After the cue manipulation, all rats were sacrificed, the dmPFC was dissected out, and DNA and mRNA were extracted. Methylated DNA was purified using methylated DNA immuno‐precipitation, and mRNA was reverse‐transcribed into cDNA; levels of each were then quantified via digital PCR procedures. Interestingly, I observed cue‐induced changes in DNA methylation within Homer2, Dlg4, Npas4, and Grin1 promoter regions. These context‐specific changes indicate that DNA methylation is much more dynamic than previously shown. Additionally, I saw changes in mRNA expression for Homer2, Dlg4, and Npas4 that appear to be highly reflective of the changes in DNA methylation. These results indicate re‐exposure to cocaine cues induce gene‐specific mRNA expression via rapid changes in DNA methylation. Support or Funding Information This research was supported by NIH grants DA‐027115 and DA‐027525 (TEK) and DA024038 (KKS), as well as funding from and the W.M. Keck Foundation (TEK). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .