Oxytocin prevents cue-induced reinstatement of oxycodone seeking: Involvement of DNA methylation in the hippocampus.
5-Methylcytosine
/ analogs & derivatives
Animals
Conditioning, Classical
/ drug effects
Cues
DNA Methylation
/ drug effects
Dose-Response Relationship, Drug
Hippocampus
/ drug effects
Learning
/ drug effects
Male
Memory
/ drug effects
Narcotic-Related Disorders
/ genetics
Oxycodone
/ pharmacology
Oxytocin
/ pharmacology
RNA, Messenger
/ drug effects
Rats
Rats, Sprague-Dawley
DNA methylation
oxycodone
oxytocin
Journal
Addiction biology
ISSN: 1369-1600
Titre abrégé: Addict Biol
Pays: United States
ID NLM: 9604935
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
26
01
2021
received:
27
11
2020
accepted:
05
02
2021
pubmed:
21
2
2021
medline:
3
2
2022
entrez:
20
2
2021
Statut:
ppublish
Résumé
Oxycodone is one of the most commonly used analgesics in the clinic. However, long-term use can contribute to drug dependence. Accumulating evidence of changes in DNA methylation after opioid relapse has provided insight into mechanisms underlying drug-associated memory. The neuropeptide oxytocin is reported to be a potential treatment for addiction. The present study sought to identify changes in global and synaptic gene methylation after cue-induced reinstatement of oxycodone conditioned place preference (CPP) and the effect of oxytocin. We analyzed hippocampal mRNA of synaptic genes and also synaptic density in response to oxycodone CPP. We determined the mRNA levels of DNA methyltransferases (Dnmts) and ten-eleven translocations (Tets), observed global 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels, and measured DNA methylation status of four synaptic genes implicated in learning and memory (Arc, Dlg1, Dlg4, and Syn1). Both synaptic density and the transcription of 15 hippocampal synaptic genes significantly increased following cue-induced reinstatement of oxycodone CPP. Oxycodone relapse was also related to markedly decreased 5-mC levels and decreased transcription of Dnmt1, Dnmt3a, and Dnmt3b; in contrast, 5-hmC levels and the transcription of Tet1 and Tet3 were increased. Oxycodone exposure induced DNA hypomethylation at the exons of the Arc, Dlg1, Dlg4, and Syn1 genes. Intracerebroventricular (ICV) administration of oxytocin (2.5 μg/μl) specifically blocked oxycodone relapse, possibly by inhibition of Arc, Dlg1, Dlg4, and Syn1 hypomethylation in oxycodone-treated rats. Together, these data indicate the occurrence of epigenetic changes in the hippocampus following oxycodone relapse and the potential role of oxytocin in oxycodone addiction.
Substances chimiques
RNA, Messenger
0
5-hydroxymethylcytosine
1123-95-1
Oxytocin
50-56-6
5-Methylcytosine
6R795CQT4H
Oxycodone
CD35PMG570
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13025Informations de copyright
© 2021 Society for the Study of Addiction.
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