Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1

Adrian Groh; Mathias Rhein; Vanessa Buchholz; Alexandra Burkert; Christian G. Huber; Undine E. Lang; Stefan J. Borgwardt; Annemarie Heberlein; Marc A.N. Muschler; Thomas Hillemacher; Stefan Bleich; Helge Frieling; Marc Walter

doi:10.1159/000486973

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1

Adrian Groh, Mathias Rhein, Vanessa Buchholz, Alexandra Burkert, Christian G. Huber, Undine E. Lang, Stefan J. Borgwardt, Annemarie Heberlein, Marc A.N. Muschler, Thomas Hillemacher, Stefan Bleich, Helge Frieling, Marc Walter

Clinic of Psychiatry and Psychotherapy

6 Citations (Scopus)

Abstract

The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro-opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.

Original language	English
Journal	Neuropsychobiology
Volume	75
Issue number	4
Pages (from-to)	193-199
Number of pages	7
ISSN	0302-282X
DOIs	https://doi.org/10.1159/000486973
Publication status	Published - 01.04.2018

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title = "Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1",

abstract = "The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro-opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.",

author = "Adrian Groh and Mathias Rhein and Vanessa Buchholz and Alexandra Burkert and Huber, {Christian G.} and Lang, {Undine E.} and Borgwardt, {Stefan J.} and Annemarie Heberlein and Muschler, {Marc A.N.} and Thomas Hillemacher and Stefan Bleich and Helge Frieling and Marc Walter",

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doi = "10.1159/000486973",

language = "English",

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T1 - Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1

AU - Groh, Adrian

AU - Rhein, Mathias

AU - Buchholz, Vanessa

AU - Burkert, Alexandra

AU - Huber, Christian G.

AU - Lang, Undine E.

AU - Borgwardt, Stefan J.

AU - Heberlein, Annemarie

AU - Muschler, Marc A.N.

AU - Hillemacher, Thomas

AU - Bleich, Stefan

AU - Frieling, Helge

AU - Walter, Marc

PY - 2018/4/1

Y1 - 2018/4/1

N2 - The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro-opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.

AB - The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro-opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.

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Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1

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