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Regulation of Brain DNA Methylation Factors and of the Orexinergic System by Cocaine and Food Self-Administration
- Source :
- Molecular Neurobiology, 56, 5315-5331. Humana Press, Molecular neurobiology, 56(8), 5315-5331. Humana Press, Molecular Neurobiology, Molecular Neurobiology, Humana Press, 2019, ⟨10.1007/s12035-018-1453-6⟩
- Publication Year :
- 2019
-
Abstract
- 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 orexin 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.
- Subjects :
- 0301 basic medicine
RNA, Messenger/genetics
Male
Orexins/metabolism
Wistar
Self Administration
Peptides/metabolism
DNA Methyltransferase 3A
0302 clinical medicine
Cocaine
Orexin Receptors
DNA (Cytosine-5-)-Methyltransferases/genetics
DNA (Cytosine-5-)-Methyltransferases
Prefrontal cortex
media_common
Regulation of gene expression
Putamen
Putamen/metabolism
Brain
Neurology
DNA methylation
medicine.drug
DNA Methylation/genetics
media_common.quotation_subject
Neuroscience (miscellaneous)
Cocaine/administration & dosage
Hypothalamus
Prefrontal Cortex
Biology
Orexin Receptors/genetics
03 medical and health sciences
Cellular and Molecular Neuroscience
Reward system
Operant
Dopamine
Proto-Oncogene Proteins
medicine
Brain/metabolism
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Epigenetics
RNA, Messenger
Rats, Wistar
Orexins
Hypothalamus/metabolism
Addiction
Feeding Behavior
DNA Methylation
Orexin
Rats
MicroRNAs/genetics
Proto-Oncogene Proteins/genetics
MicroRNAs
030104 developmental biology
Gene Expression Regulation
Food
RNA
Messenger/genetics
Conditioning, Operant
Peptides
Neuroscience
030217 neurology & neurosurgery
Prefrontal Cortex/metabolism
Conditioning
Subjects
Details
- Language :
- English
- ISSN :
- 08937648
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....b4c145e54647ae174c176e84b3de87c2