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Reversal of Cocaine-Conditioned Place Preference through Methyl Supplementation in Mice: Altering Global DNA Methylation in the Prefrontal Cortex

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Title: Reversal of Cocaine-Conditioned Place Preference through Methyl Supplementation in Mice: Altering Global DNA Methylation in the Prefrontal Cortex
Authors: Tian, Weiping, Zhao, Mei, Li, Min, Song, Tianbao, Zhang, Min, Quan, Li, Li, Shengbin, Sun, Zhong Sheng, Tian, WP (reprint author), Xi An Jiao Tong Univ, Sch Med, Dept Forens Sci, Xian 710049, Shanxi, Peoples R China.
Source: PLoS One
PLoS ONE, Vol 7, Iss 3, p e33435 (2012)
Publisher Information: Public Library of Science (PLoS), 2012.
Publication Year: 2012
Subject Terms: Male, 0301 basic medicine, Science, Prefrontal Cortex, Nucleus Accumbens, Cocaine-Related Disorders, Mice, 03 medical and health sciences, Methionine, Reward, Conditioning, Psychological, Animals, DNA (Cytosine-5-)-Methyltransferases, RNA, Messenger, Base Sequence, DNA Methylation, Physiological Psychology/biological Psychology, DNA-Binding Proteins, Mice, Inbred C57BL, Food, Medicine, Morphine Dependence, Research Article
Description: Analysis of global methylation in cells has revealed correlations between overall DNA methylation status and some biological states. Recent studies suggest that epigenetic regulation through DNA methylation could be responsible for neuroadaptations induced by addictive drugs. However, there is no investigation to determine global DNA methylation status following repeated exposure to addictive drugs. Using mice conditioned place preference (CPP) procedure, we measured global DNA methylation level in the nucleus accumbens (NAc) and the prefrontal cortex (PFC) associated with drug rewarding effects. We found that cocaine-, but not morphine- or food-CPP training decreased global DNA methylation in the PFC. Chronic treatment with methionine, a methyl donor, for 25 consecutive days prior to and during CPP training inhibited the establishment of cocaine, but not morphine or food CPP. We also found that both mRNA and protein level of DNMT (DNA methytransferase) 3b in the PFC were downregulated following the establishment of cocaine CPP, and the downregulation could be reversed by repeated administration of methionine. Our study indicates a crucial role of global PFC DNA hypomethylation in the rewarding effects of cocaine. Reversal of global DNA hypomethylation could significantly attenuate the rewarding effects induced by cocaine. Our results suggest that methionine may have become a potential therapeutic target to treat cocaine addiction.
Document Type: Article
Other literature type
Language: English
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0033435
Access URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033435&type=printable
https://pubmed.ncbi.nlm.nih.gov/22438930
https://doaj.org/article/aa5c48dda7634286b8cd3ad59e28ba97
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033435
https://pubmed.ncbi.nlm.nih.gov/22438930/
http://ir.psych.ac.cn/handle/311026/13248
http://www.irgrid.ac.cn/handle/1471x/970994
http://ui.adsabs.harvard.edu/abs/2012PLoSO...733435T/abstract
Rights: CC BY
Accession Number: edsair.doi.dedup.....7a186f0b4ce886a697b82700a59ef7f1
Database: OpenAIRE
Description
Abstract:Analysis of global methylation in cells has revealed correlations between overall DNA methylation status and some biological states. Recent studies suggest that epigenetic regulation through DNA methylation could be responsible for neuroadaptations induced by addictive drugs. However, there is no investigation to determine global DNA methylation status following repeated exposure to addictive drugs. Using mice conditioned place preference (CPP) procedure, we measured global DNA methylation level in the nucleus accumbens (NAc) and the prefrontal cortex (PFC) associated with drug rewarding effects. We found that cocaine-, but not morphine- or food-CPP training decreased global DNA methylation in the PFC. Chronic treatment with methionine, a methyl donor, for 25 consecutive days prior to and during CPP training inhibited the establishment of cocaine, but not morphine or food CPP. We also found that both mRNA and protein level of DNMT (DNA methytransferase) 3b in the PFC were downregulated following the establishment of cocaine CPP, and the downregulation could be reversed by repeated administration of methionine. Our study indicates a crucial role of global PFC DNA hypomethylation in the rewarding effects of cocaine. Reversal of global DNA hypomethylation could significantly attenuate the rewarding effects induced by cocaine. Our results suggest that methionine may have become a potential therapeutic target to treat cocaine addiction.
ISSN:19326203
DOI:10.1371/journal.pone.0033435