Abstract
Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain. In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein. While high or low μ-opioid receptor expression significantly correlated with local OPRM1 mRNA levels, there was no corresponding association with OPRM1 methylation status. Additional experiments in human cell lines showed that changes in DNA methylation associated with changes in μ-opioid expression were an order of magnitude greater than differences in brain. Hence, different degrees of DNA methylation associated with chronic opioid exposure are unlikely to exert a major role in the region-specificity of μ-opioid receptor expression in the human brain.
Highlights
ObjectivesExposure to opioids has been associated with epigenetic effects
Human cell lines with different μ-opioid receptor expression differed by 30–80% with respect to the OPRM1 methylation, suggesting the possibility that OPRM1 expression in humans can be regulated via DNA methylation
Following observations that exposure to opioids triggers epigenetic modifications [1,22,23,57], we analyzed whether such effects contribute to the differential expression of μ-opioid receptors across the human brain
Summary
Exposure to opioids has been associated with epigenetic effects
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