PMID- 28597409
OWN - NLM
STAT- MEDLINE
DCOM- 20180807
LR  - 20181113
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 32
IP  - 4
DP  - 2017 Nov
TI  - Progression and Persistence of Neurotoxicity Induced by MDMA in Dopaminergic 
      Regions of the Mouse Brain and Association with Noradrenergic, GABAergic, and 
      Serotonergic Damage.
PG  - 563-574
LID - 10.1007/s12640-017-9761-6 [doi]
AB  - The amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) is known to 
      induce neurotoxic damage in dopaminergic regions of the mouse brain. In order to 
      characterize how the number of administrations influenced the severity of 
      MDMA-induced dopaminergic damage and to describe the localization and persistence 
      of this damage, we evaluated the changes in tyrosine hydroxylase (TH) and 
      dopamine transporter (DAT) in different regions of the mouse brain. Moreover, we 
      investigated whether dopaminergic damage was associated with noradrenergic, 
      GABAergic, and serotonergic damage, by evaluating the changes in noradrenaline 
      transporter (NET), glutamic acid decarboxylase-67 (GAD-67), and serotonin 
      transporter (SERT). Mice received 14, 28, or 36 MDMA administrations (10 mg/kg 
      twice a week) and were sacrificed at different time points (postnatal days 85, 
      110, 138, or 214) for immunohistochemical evaluation. Mice receiving 28 
      administrations showed reduced levels of DAT-positive fibers in caudate-putamen 
      (CPu) and medial prefrontal cortex (mPFC) and reduced levels of TH-positive 
      nigral neurons. These mice also displayed increased NET-positive hippocampal 
      fibers, reduced GAD-67-positive neurons in CPu and hippocampus, and reduced 
      GAD-67-positive fibers in mPFC. Similar effects of MDMA on DAT, TH, and GAD-67 
      were found in mice receiving 36 administrations, which also displayed reduced 
      levels of striatal, cortical, and hippocampal TH-immunoreactive fibers. The 
      reductions in dopaminergic markers and GAD-67 persisted at 3 months after MDMA 
      discontinuation. Finally, MDMA never modified the levels of SERT. These results 
      provide further insight into the localization and persistence of MDMA-induced 
      dopaminergic damage and show that this effect may associate with GABAergic but 
      not noradrenergic or serotonergic damage.
FAU - Costa, Giulia
AU  - Costa G
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
FAU - Morelli, Micaela
AU  - Morelli M
AUID- ORCID: 0000-0003-0394-5782
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. morelli@unica.it.
AD  - National Research Council of Italy, Neuroscience Institute, Cagliari, Italy. 
      morelli@unica.it.
FAU - Simola, Nicola
AU  - Simola N
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy.
LA  - eng
GR  - Legge Regionale 7 Agosto 2007, N.7, annualita 2008 and 2010/Regione Autonoma 
      della Sardegna/
PT  - Journal Article
DEP - 20170609
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adrenergic Neurons/*drug effects
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Corpus Striatum/drug effects
MH  - Dopamine/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/drug effects/metabolism
MH  - GABAergic Neurons/*drug effects
MH  - Male
MH  - Mice, Inbred C57BL
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neurons/drug effects
MH  - Neurotoxicity Syndromes/drug therapy
MH  - Serotonergic Neurons/*drug effects
MH  - Serotonin Plasma Membrane Transport Proteins/drug effects
MH  - Tyrosine 3-Monooxygenase/metabolism
OTO - NOTNLM
OT  - Amphetamine-related drugs
OT  - Dopamine transporter
OT  - Glutamic acid decarboxylase-67
OT  - Noradrenaline transporter
OT  - Serotonin transporter
OT  - Tyrosine hydroxylase
EDAT- 2017/06/10 06:00
MHDA- 2018/08/08 06:00
CRDT- 2017/06/10 06:00
PHST- 2017/03/10 00:00 [received]
PHST- 2017/05/24 00:00 [accepted]
PHST- 2017/05/17 00:00 [revised]
PHST- 2017/06/10 06:00 [pubmed]
PHST- 2018/08/08 06:00 [medline]
PHST- 2017/06/10 06:00 [entrez]
AID - 10.1007/s12640-017-9761-6 [pii]
AID - 10.1007/s12640-017-9761-6 [doi]
PST - ppublish
SO  - Neurotox Res. 2017 Nov;32(4):563-574. doi: 10.1007/s12640-017-9761-6. Epub 2017 
      Jun 9.