PMID- 25643298
OWN - NLM
STAT- MEDLINE
DCOM- 20150420
LR  - 20181113
IS  - 1546-1726 (Electronic)
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 18
IP  - 3
DP  - 2015 Mar
TI  - Epigenetic basis of opiate suppression of Bdnf gene expression in the ventral 
      tegmental area.
PG  - 415-22
LID - 10.1038/nn.3932 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) has a crucial role in modulating neural 
      and behavioral plasticity to drugs of abuse. We found a persistent downregulation 
      of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response 
      to chronic opiate exposure, which was mediated by specific epigenetic 
      modifications at the corresponding Bdnf gene promoters. Exposure to chronic 
      morphine increased stalling of RNA polymerase II at these Bdnf promoters in VTA 
      and altered permissive and repressive histone modifications and occupancy of 
      their regulatory proteins at the specific promoters. Furthermore, we found that 
      morphine suppressed binding of phospho-CREB (cAMP response element binding 
      protein) to Bdnf promoters in VTA, which resulted from enrichment of 
      trimethylated H3K27 at the promoters, and that decreased NURR1 (nuclear receptor 
      related-1) expression also contributed to Bdnf repression and associated 
      behavioral plasticity to morphine. Our findings suggest previously unknown 
      epigenetic mechanisms of morphine-induced molecular and behavioral 
      neuroadaptations.
FAU - Koo, Ja Wook
AU  - Koo JW
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Mazei-Robison, Michelle S
AU  - Mazei-Robison MS
AD  - 1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School 
      of Medicine at Mount Sinai, New York, New York, USA. [2] Department of 
      Physiology, Michigan State University, East Lansing, Michigan, USA.
FAU - LaPlant, Quincey
AU  - LaPlant Q
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Egervari, Gabor
AU  - Egervari G
AD  - 1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School 
      of Medicine at Mount Sinai, New York, New York, USA. [2] Department of 
      Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] 
      Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at 
      Mount Sinai, New York, New York, USA.
FAU - Braunscheidel, Kevin M
AU  - Braunscheidel KM
AD  - Department of Pharmacology and Toxicology, The State University of New York at 
      Buffalo, Buffalo, New York, USA.
FAU - Adank, Danielle N
AU  - Adank DN
AD  - Department of Pharmacology and Toxicology, The State University of New York at 
      Buffalo, Buffalo, New York, USA.
FAU - Ferguson, Deveroux
AU  - Ferguson D
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Feng, Jian
AU  - Feng J
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Sun, Haosheng
AU  - Sun H
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Scobie, Kimberly N
AU  - Scobie KN
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Damez-Werno, Diane M
AU  - Damez-Werno DM
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Ribeiro, Efrain
AU  - Ribeiro E
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Pena, Catherine Jensen
AU  - Pena CJ
AUID- ORCID: 0000000228845035
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Walker, Deena
AU  - Walker D
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Bagot, Rosemary C
AU  - Bagot RC
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Cahill, Michael E
AU  - Cahill ME
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Anderson, Sarah Ann R
AU  - Anderson SA
AD  - 1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School 
      of Medicine at Mount Sinai, New York, New York, USA. [2] Department of 
      Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] 
      Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at 
      Mount Sinai, New York, New York, USA.
FAU - Labonte, Benoit
AU  - Labonte B
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Hodes, Georgia E
AU  - Hodes GE
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Browne, Heidi
AU  - Browne H
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Chadwick, Benjamin
AU  - Chadwick B
AD  - 1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School 
      of Medicine at Mount Sinai, New York, New York, USA. [2] Department of 
      Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] 
      Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at 
      Mount Sinai, New York, New York, USA.
FAU - Robison, Alfred J
AU  - Robison AJ
AD  - 1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School 
      of Medicine at Mount Sinai, New York, New York, USA. [2] Department of 
      Physiology, Michigan State University, East Lansing, Michigan, USA.
FAU - Vialou, Vincent F
AU  - Vialou VF
AD  - 1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School 
      of Medicine at Mount Sinai, New York, New York, USA. [2] Institut National de la 
      Sante et de la Recherche Medicale, U952, Centre National de la Recherche 
      Scientifique, Unite Mixte de Recherche 7224, UPMC, Paris, France.
FAU - Dias, Caroline
AU  - Dias C
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Lorsch, Zachary
AU  - Lorsch Z
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Mouzon, Ezekiell
AU  - Mouzon E
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Lobo, Mary Kay
AU  - Lobo MK
AD  - Department of Anatomy and Neurobiology, University of Maryland School of 
      Medicine, Baltimore, Maryland, USA.
FAU - Dietz, David M
AU  - Dietz DM
AD  - Institut National de la Sante et de la Recherche Medicale, U952, Centre National 
      de la Recherche Scientifique, Unite Mixte de Recherche 7224, UPMC, Paris, France.
FAU - Russo, Scott J
AU  - Russo SJ
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
FAU - Neve, Rachael L
AU  - Neve RL
AD  - Department of Brain and Cognitive Sciences, Massachusetts Institute of 
      Technology, Cambridge, Massachusetts, USA.
FAU - Hurd, Yasmin L
AU  - Hurd YL
AD  - 1] Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School 
      of Medicine at Mount Sinai, New York, New York, USA. [2] Department of 
      Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [3] 
      Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at 
      Mount Sinai, New York, New York, USA.
FAU - Nestler, Eric J
AU  - Nestler EJ
AD  - Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of 
      Medicine at Mount Sinai, New York, New York, USA.
LA  - eng
GR  - T32 DA007135/DA/NIDA NIH HHS/United States
GR  - P01 DA008227/DA/NIDA NIH HHS/United States
GR  - R01 DA015446/DA/NIDA NIH HHS/United States
GR  - R01 DA038613/DA/NIDA NIH HHS/United States
GR  - R01 DA014133/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150202
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 2.1.1.43 (Ezh2 protein, mouse)
RN  - EC 2.1.1.43 (Polycomb Repressive Complex 2)
RN  - EC 2.7.7.- (RNA Polymerase II)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
CIN - Nat Rev Neurosci. 2015 Apr;16(4):186-7. PMID: 25736021
MH  - Analgesics, Opioid/*metabolism/pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cocaine/pharmacology
MH  - Conditioning, Operant/drug effects
MH  - Dopamine Uptake Inhibitors/pharmacology
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - Epigenesis, Genetic/drug effects/*physiology
MH  - Heroin Dependence/pathology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Motor Activity/drug effects/genetics
MH  - Polycomb Repressive Complex 2/genetics/metabolism
MH  - Postmortem Changes
MH  - RNA Polymerase II/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ventral Tegmental Area/drug effects/*metabolism
PMC - PMC4340719
MID - NIHMS651676
COIS- Competing Financial Interests: The authors declare no competing financial 
      interests.
EDAT- 2015/02/03 06:00
MHDA- 2015/04/22 06:00
PMCR- 2015/09/01
CRDT- 2015/02/03 06:00
PHST- 2014/10/15 00:00 [received]
PHST- 2014/12/22 00:00 [accepted]
PHST- 2015/02/03 06:00 [entrez]
PHST- 2015/02/03 06:00 [pubmed]
PHST- 2015/04/22 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - nn.3932 [pii]
AID - 10.1038/nn.3932 [doi]
PST - ppublish
SO  - Nat Neurosci. 2015 Mar;18(3):415-22. doi: 10.1038/nn.3932. Epub 2015 Feb 2.