PMID- 29629511
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 34
IP  - 4
DP  - 2018 Nov
TI  - Repeated Administration of 3,4-Methylenedioxymethamphetamine (MDMA) Elevates the 
      Levels of Neuronal Nitric Oxide Synthase in the Nigrostriatal System: Possible 
      Relevance to Neurotoxicity.
PG  - 763-768
LID - 10.1007/s12640-018-9892-4 [doi]
AB  - Previous studies have consistently demonstrated that the amphetamine-related drug 
      3,4-methylenedioxymethamphetamine (MDMA) induces dopaminergic damage in the mouse 
      brain, and that this effect is most marked in the nigrostriatal system. Moreover, 
      it has been suggested that the overproduction of nitric oxide (NO) may 
      participate in the dopaminergic damage induced by MDMA. To further elucidate this 
      issue, we evaluated the levels of the enzyme nitric oxide synthase (nNOS), which 
      catalyzes the production of NO, in mice treated with regimens of MDMA that induce 
      progressive and persistent neurotoxicity in the dopaminergic nigrostriatal 
      system. Mice received 14, 28, or 36 administrations of MDMA (10 mg/kg i.p.), 
      twice a day/twice a week, and were sacrificed at different time-points after 
      treatment discontinuation. Thereafter, the number of nNOS-positive neurons was 
      quantified by immunohistochemistry in the caudate-putamen (CPu) and substantia 
      nigra pars compacta (SNc). MDMA elevated the numbers of nNOS-positive neurons in 
      the CPu of mice that received 28 or 36 drug administrations. This effect was 
      still detectable at 3 months after treatment discontinuation. Moreover, MDMA 
      elevated the numbers of nNOS-positive neurons in the SNc. However, this effect 
      occurred only in mice that received 28 drug administrations and were sacrificed 
      3 days after treatment discontinuation. These results are in line with the 
      hypothesis that activation of the NO cascade participates in the toxic effects 
      induced by MDMA in the dopaminergic nigrostriatal system. Moreover, they suggest 
      that activation of the NO cascade induces toxic effects that are more marked in 
      striatal terminals, compared with nigral neurons.
FAU - Costa, Giulia
AU  - Costa G
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Building A, Monserrato University Campus, SP 8, Km 0.700, 09042, 
      Monserrato, Italy.
FAU - Morelli, Micaela
AU  - Morelli M
AUID- ORCID: 0000-0003-0394-5782
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Building A, Monserrato University Campus, SP 8, Km 0.700, 09042, 
      Monserrato, Italy. morelli@unica.it.
AD  - National Research Council of Italy (CNR), Neuroscience Institute, Cagliari, 
      Italy. morelli@unica.it.
AD  - National Institute of Neuroscience (INN), University of Cagliari, Cagliari, 
      Italy. morelli@unica.it.
FAU - Simola, Nicola
AU  - Simola N
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Building A, Monserrato University Campus, SP 8, Km 0.700, 09042, 
      Monserrato, Italy.
AD  - National Institute of Neuroscience (INN), University of Cagliari, Cagliari, 
      Italy.
LA  - eng
GR  - Legge Regionale 7 Agosto 2007, N.7, annualita 2008 and 2010/Regione Autonoma 
      della Sardegna/
GR  - D.R. n.159 del 18.11.2016/University of Cagliari/
GR  - project 2016.0845/Fondazione di Sardegna (IT)/
PT  - Journal Article
DEP - 20180409
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, mouse)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Caudate Nucleus/*drug effects/enzymology/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurons/drug effects/enzymology/pathology
MH  - Nitric Oxide Synthase Type I/*metabolism
MH  - Pars Compacta/*drug effects/enzymology/pathology
MH  - Putamen/*drug effects/enzymology/pathology
MH  - Random Allocation
OTO - NOTNLM
OT  - Amphetamine-related drugs
OT  - Caudate-putamen
OT  - Neurotoxicity
OT  - Substantia nigra pars compacta
EDAT- 2018/04/10 06:00
MHDA- 2018/11/27 06:00
CRDT- 2018/04/10 06:00
PHST- 2017/10/24 00:00 [received]
PHST- 2018/03/20 00:00 [accepted]
PHST- 2018/03/01 00:00 [revised]
PHST- 2018/04/10 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/04/10 06:00 [entrez]
AID - 10.1007/s12640-018-9892-4 [pii]
AID - 10.1007/s12640-018-9892-4 [doi]
PST - ppublish
SO  - Neurotox Res. 2018 Nov;34(4):763-768. doi: 10.1007/s12640-018-9892-4. Epub 2018 
      Apr 9.