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Regulation of Brain DNA Methylation Factors and of the Orexinergic System by Cocaine and Food Self-Administration
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Regulation of Brain DNA Methylation Factors and of the Orexinergic System by Cocaine and Food Self-Administration
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Journal Article
Regulation of Brain DNA Methylation Factors and of the Orexinergic System by Cocaine and Food Self-Administration
2019
Overview
Inhibitors of DNA methylation and orexin type-1 receptor antagonists modulate the neurobiological effects driving drugs of abuse and natural reinforcers by activating common brain structures of the mesolimbic reward system. In this study, we applied a self-administration paradigm to assess the involvement of factors regulating DNA methylation processes and satiety or appetite signals. These factors include Dnmts and Tets, miR-212/132, orexins, and orx-R1 genes
.
The study focused on dopamine projection areas such as the prefrontal cortex (PFCx) and caudate putamen (CPu) and in the hypothalamus (HP) that is interconnected with the reward system. Striking changes were observed in response to both reinforcers, but differed depending on contingent and non-contingent delivery. Expression also differed in the PFCx and the CPu. Cocaine and food induced opposite effects on
Dnmt3a
expression in both brain structures, whereas they repressed both miRs to a different extent, without affecting their primary transcript in the CPu. Unexpectedly, orexin mRNAs were found in the CPu, suggesting a transport from their transcription site in the HP. The o
rexin receptor1
gene was found to be induced by cocaine in the PFCx, consistent with a regulation by DNA methylation. Global levels of 5-methylcytosines in the PFCx were not significantly altered by cocaine, suggesting that it is rather their distribution that contributes to long-lasting behaviors. Together, our data demonstrate that DNA methylation regulating factors are differentially altered by cocaine and food. At the molecular level, they support the idea that neural circuits activated by both reinforcers do not completely overlap.
Publisher
Springer US,Springer Nature B.V,Springer
Subject
/ Appetite
/ Biochemistry, Molecular Biology
/ Biomedical and Life Sciences
/ Cocaine
/ Cocaine - administration & dosage
/ DNA
/ DNA (Cytosine-5-)-Methyltransferases - genetics
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ Dopamine
/ Food
/ Male
/ Orexin Receptors - metabolism
/ Orexins
/ Prefrontal Cortex - metabolism
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Putamen
/ Satiety
