PMID- 27989838
OWN - NLM
STAT- MEDLINE
DCOM- 20171226
LR  - 20231213
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 114
DP  - 2016 Dec
TI  - Opioid gene expression changes and post-translational histone modifications at 
      promoter regions in the rat nucleus accumbens after acute and repeated 
      3,4-methylenedioxy-methamphetamine (MDMA) exposure.
PG  - 209-218
LID - S1043-6618(16)30518-7 [pii]
LID - 10.1016/j.phrs.2016.10.023 [doi]
AB  - The recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has been 
      shown to produce neurotoxic damage and long-lasting changes in several brain 
      areas. In addition to the involvement of serotoninergic and dopaminergic systems, 
      little information exists about the contribution of nociceptin/orphaninFQ 
      (N/OFQ)-NOP and dynorphin (DYN)-KOP systems in neuronal adaptations evoked by 
      MDMA. Here we investigated the behavioral and molecular effects induced by acute 
      (8mg/kg) or repeated (8mg/kg twice daily for seven days) MDMA exposure. MDMA 
      exposure affected body weight gain and induced hyperlocomotion; this latter 
      effect progressively decreased after repeated administration. Gene expression 
      analysis indicated a down-regulation of the N/OFQ system and an up-regulation of 
      the DYN system in the nucleus accumbens (NAc), highlighting an opposite systems 
      regulation in response to MDMA exposure. Since histone modifications have been 
      strongly associated to the addiction-related maladaptive changes, we examined two 
      permissive (acH3K9 and me3H3K4) and two repressive transcription marks (me3H3K27 
      and me2H3K9) at the pertinent opioid gene promoter regions. Chromatin 
      immunoprecipitation assays revealed that acute MDMA increased me3H3K4 at the 
      pN/OFQ, pDYN and NOP promoters. Following acute and repeated treatment a 
      significant decrease of acH3K9 at the pN/OFQ promoter was observed, which 
      correlated with gene expression results. Acute treatment caused an acH3K9 
      increase and a me2H3K9 decrease at the pDYN promoter which matched its mRNA 
      up-regulation. Our data indicate that the activation of the DYNergic stress 
      system together with the inactivation of the N/OFQergic anti-stress system 
      contribute to the neuroadaptive actions of MDMA and offer novel epigenetic 
      information associated with MDMA abuse.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Caputi, Francesca Felicia
AU  - Caputi FF
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of 
      Bologna, Irnerio 48, 40126 Bologna, Italy.
FAU - Palmisano, Martina
AU  - Palmisano M
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of 
      Bologna, Irnerio 48, 40126 Bologna, Italy.
FAU - Carboni, Lucia
AU  - Carboni L
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of 
      Bologna, Irnerio 48, 40126 Bologna, Italy.
FAU - Candeletti, Sanzio
AU  - Candeletti S
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of 
      Bologna, Irnerio 48, 40126 Bologna, Italy.
FAU - Romualdi, Patrizia
AU  - Romualdi P
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of 
      Bologna, Irnerio 48, 40126 Bologna, Italy. Electronic address: 
      patrizia.romualdi@unibo.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161029
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Opioid Peptides)
RN  - 0 (Serotonin Agents)
RN  - 74913-18-1 (Dynorphins)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/administration & dosage/pharmacology
MH  - Animals
MH  - Dynorphins/*genetics
MH  - Gene Expression Regulation/drug effects
MH  - Histone Code/*drug effects
MH  - Locomotion/drug effects
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology
MH  - Nucleus Accumbens/*drug effects/metabolism
MH  - Opioid Peptides/*genetics
MH  - Promoter Regions, Genetic/drug effects
MH  - Rats, Sprague-Dawley
MH  - Serotonin Agents/administration & dosage/*pharmacology
MH  - Nociceptin
OTO - NOTNLM
OT  - Dynorphin
OT  - Epigenetics
OT  - Histone modification
OT  - MDMA
OT  - Nociceptin
OT  - Opioid system
EDAT- 2016/12/19 06:00
MHDA- 2017/12/27 06:00
CRDT- 2016/12/20 06:00
PHST- 2016/05/30 00:00 [received]
PHST- 2016/07/29 00:00 [revised]
PHST- 2016/10/28 00:00 [accepted]
PHST- 2016/12/19 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
PHST- 2016/12/20 06:00 [entrez]
AID - S1043-6618(16)30518-7 [pii]
AID - 10.1016/j.phrs.2016.10.023 [doi]
PST - ppublish
SO  - Pharmacol Res. 2016 Dec;114:209-218. doi: 10.1016/j.phrs.2016.10.023. Epub 2016 
      Oct 29.