PMID- 32067070
OWN - NLM
STAT- MEDLINE
DCOM- 20210310
LR  - 20210310
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 94
IP  - 3
DP  - 2020 Mar
TI  - Dose concentration and spatial memory and brain mitochondrial function 
      association after 3,4-methylenedioxymethamphetamine (MDMA) administration in 
      rats.
PG  - 911-925
LID - 10.1007/s00204-020-02673-x [doi]
AB  - MDMA-induced impairments of memory performance have been reported in different 
      human and animal studies. However, the correlation between spatial memory 
      impairment, brain mitochondrial function, and concentrations of MDMA and its 
      metabolites has not yet been investigated despite it being needed for comparison 
      with human studies. Therefore, the aim of this study was to investigate the dose 
      concentration and spatial memory as well as brain mitochondrial function 
      association after MDMA administration in rats. We assessed the effects of MDMA 
      [0.5, 2.5, 5, 10 and 15 mg/kg; intraperitoneally (I.P)] on spatial memory of male 
      Wistar rats in the Morris water maze test (MWM) and brain mitochondrial function 
      (i.e., reactive oxygen species, mitochondrial membrane potential, swelling and 
      outer membrane damage, cytochrome c release, and ADP/ATP ratio). Concentrations 
      of MDMA and its metabolite, MDA, were determined in plasma, cerebrospinal fluid 
      (CSF) and brain which was obtained immediately after probe test of MWM (i.e., 4 h 
      after last training trial). The results of this study indicate nonlinear kinetics 
      of MDMA after I.P adminstration. Also, an insignificant correlation was observed 
      between MDMA doses and the MDA/MDMA ratio in plasma, CSF, and brain. Moreover, 
      the results showed that MDMA, but not MDA, accumulated in brain tissue by 
      increasing the administered doses. Beside, MDMA-induced impairments of spatial 
      memory and brain mitochondrial function were significantly correlated with the 
      concentrations of both MDMA and MDA in plasma, CSF, and brain. Therefore, it can 
      be suggested that MDMA and its metabolite, MDA, affect spatial memory and brain 
      mitochondrial function.
FAU - Taghizadeh, G
AU  - Taghizadeh G
AD  - Rehabilitation Research Center, Department of Occupational Therapy, School of 
      Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran.
FAU - Mehdizadeh, H
AU  - Mehdizadeh H
AD  - Department of Neurosciences, School of Advanced Technologies in Medicine, Tehran 
      University of Medical Sciences, Tehran, Iran.
FAU - Lavasani, H
AU  - Lavasani H
AD  - Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, 
      Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
FAU - Hosseinzadeh Ardakani, Y
AU  - Hosseinzadeh Ardakani Y
AD  - Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, 
      Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
FAU - Foroumadi, A
AU  - Foroumadi A
AD  - Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran 
      University of Medical Sciences, Tehran, Iran.
FAU - Halvaei Khankahdani, Z
AU  - Halvaei Khankahdani Z
AD  - Faculty of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran.
FAU - Moshtagh, A
AU  - Moshtagh A
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, Tehran, Iran.
FAU - Pourahmad, J
AU  - Pourahmad J
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Sharifzadeh, M
AU  - Sharifzadeh M
AUID- ORCID: 0000-0001-9171-468X
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, Tehran, Iran. msharifzadeh@sina.tums.ac.ir.
FAU - Rouini, M R
AU  - Rouini MR
AD  - Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, 
      Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 
      rouini@tums.ac.ir.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200218
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Hallucinogens)
RN  - 0 (Reactive Oxygen Species)
RN  - 333DO1RDJY (Serotonin)
RN  - 9007-43-6 (Cytochromes c)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain
MH  - Cognition
MH  - Cytochromes c
MH  - Dose-Response Relationship, Drug
MH  - Hallucinogens/*toxicity
MH  - Humans
MH  - Male
MH  - Maze Learning
MH  - Membrane Potential, Mitochondrial
MH  - Memory Disorders
MH  - Mitochondria
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species
MH  - Serotonin
MH  - Spatial Memory/*drug effects
OTO - NOTNLM
OT  - 3,4-Methylenedioxyamphetamine (MDA)
OT  - 3,4-Methylenedioxymethamphetamine (MDMA)
OT  - Dose concentration
OT  - HPLC
OT  - Mitochondria
OT  - Spatial memory
EDAT- 2020/02/19 06:00
MHDA- 2021/03/11 06:00
CRDT- 2020/02/19 06:00
PHST- 2019/10/31 00:00 [received]
PHST- 2020/02/11 00:00 [accepted]
PHST- 2020/02/19 06:00 [pubmed]
PHST- 2021/03/11 06:00 [medline]
PHST- 2020/02/19 06:00 [entrez]
AID - 10.1007/s00204-020-02673-x [pii]
AID - 10.1007/s00204-020-02673-x [doi]
PST - ppublish
SO  - Arch Toxicol. 2020 Mar;94(3):911-925. doi: 10.1007/s00204-020-02673-x. Epub 2020 
      Feb 18.