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The effect of morphine upon DNA methylation in ten regions of the rat brain

Barrow, Timothy, Byun, HM, Li, X, Smart, C, Wang, YX, Zhang, Y, Baccarelli, A and Guo, L (2018) The effect of morphine upon DNA methylation in ten regions of the rat brain. Epigenetics, 12 (12). pp. 1038-1047. ISSN 1559-2294

Item Type: Article

Abstract

Morphine is one of the most effective analgesics in medicine. However, its use is associated with the development of tolerance and dependence. Recent studies demonstrating epigenetic changes in the brain after exposure to opiates have provided insight into mechanisms possibly underlying addiction. In this study, we sought to identify epigenetic changes in ten regions of the rat brain following acute and chronic morphine exposure. We analyzed DNA methylation of six nuclear-encoded genes implicated in brain function (Bdnf, Comt, Il1b, Il6, Nr3c1 and Tnf) and three mitochondrially-encoded genes (Mtco1, Mtco2 and Mtco3), and measured global 5-methylcytosine (5-mc) and 5-hydroxymethylcytosine (5-hmc) levels. We observed differential methylation of Bdnf and Il6 in the pons, Nr3c1 in the cerebellum, and Il1b in the hippocampus in response to acute morphine exposure (all p<0.05). Chronic exposure was associated with differential methylation of Bdnf and Comt in the pons, Nr3c1 in the hippocampus and Il1b in the medulla oblongata (all p<0.05). Global 5-mc levels significantly decreased in the superior colliculus following both acute and chronic morphine exposure, and increased in the hypothalamus following chronic exposure. Chronic exposure was also associated with significantly increased global 5-hmc levels in the cerebral cortex, hippocampus and hypothalamus, but significantly decreased in the midbrain. Our results demonstrate, for the first time, highly localized epigenetic changes in the rat brain following acute and chronic morphine exposure. Further work is required to elucidate the potential role of these changes in the formation of tolerance and dependence.

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More Information

Depositing User: Timothy Barrow

Identifiers

Item ID: 8779
Identification Number: https://doi.org/10.1080/15592294.2017
ISSN: 1559-2294
URI: http://sure.sunderland.ac.uk/id/eprint/8779

Users with ORCIDS

ORCID for Timothy Barrow: ORCID iD orcid.org/0000-0003-4551-3857

Catalogue record

Date Deposited: 19 Feb 2018 14:28
Last Modified: 18 Dec 2019 16:05

Contributors

Author: Timothy Barrow ORCID iD
Author: HM Byun
Author: X Li
Author: C Smart
Author: YX Wang
Author: Y Zhang
Author: A Baccarelli
Author: L Guo

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

Subjects

Sciences > Biomedical Sciences

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