PMID- 32103463
OWN - NLM
STAT- MEDLINE
DCOM- 20210218
LR  - 20210218
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 38
IP  - 1
DP  - 2020 Jun
TI  - Bucladesine Attenuates Spatial Learning and Hippocampal Mitochondrial Impairments 
      Induced by 3, 4-Methylenedioxymethamphetamine (MDMA).
PG  - 38-49
LID - 10.1007/s12640-020-00183-3 [doi]
AB  - Neurotoxic effects of systemic administration of 3, 4- 
      methylenedioxymethamphetamine (MDMA) has been attributed to MDMA and its 
      metabolites. However, the role of the parent compound in MDMA-induced 
      mitochondrial and memory impairment has not yet been investigated. Moreover, it 
      is not yet studied that analogs of 3', 5'-cyclic adenosine monophosphate (cAMP) 
      could decrease these neurotoxic effects of MDMA. We wished to investigate the 
      effects of the central administration of MDMA on spatial memory and mitochondrial 
      function as well as the effects of bucladesine, a membrane-permeable analog of 
      cAMP, on these effects of MDMA. We assessed the effects of pre-training bilateral 
      intrahippocampal infusion of MDMA (0.01, 0.1, 0.5, and 1 mug/side), bucladesine 
      (10 and 100 muM) or combination of them on spatial memory, and different 
      parameters of hippocampal mitochondrial function including the level of reactive 
      oxygen species (ROS) production, mitochondrial membrane potential (MMP), 
      mitochondrial swelling, mitochondrial outer membrane damage, the amount of 
      cytochrome c release as well as hippocampal ADP/ATP ratio. The results showed 
      that MDMA caused spatial memory impairments as well as mitochondrial dysfunction 
      as evidenced by the marked increase in hippocampal ADP/ATP ratio, ROS level, the 
      collapse of MMP, mitochondrial swelling, and mitochondrial outer membrane damage 
      leading to cytochrome c release from the mitochondria. The current study also 
      found that bucladesine markedly reduced the destructive effects of MDMA. These 
      results provide evidence of the role of the parent compound (MDMA) in 
      MDMA-induced memory impairments through mitochondrial dysfunction. This study 
      highlights the role of cAMP/PKA signaling in MDMA-induced memory and 
      mitochondrial defects.
FAU - Taghizadeh, Ghorban
AU  - Taghizadeh G
AD  - Rehabilitation Research Center, Department of Occupational Therapy, School of 
      Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran.
FAU - Mehdizadeh, Hajar
AU  - Mehdizadeh H
AD  - Department of Neurosciences, School of Advanced Technologies in Medicine, Tehran 
      University of Medical Sciences, Tehran, Iran.
FAU - Pourahmad, Jalal
AU  - Pourahmad J
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Foroumadi, Alireza
AU  - Foroumadi A
AD  - Toxicology and Disease group, The Institute of Pharmaceutical Sciences (TIPS), 
      Tehran University of Medical Sciences, Tehran, Iran.
FAU - Hassani, Shokoufeh
AU  - Hassani S
AD  - Toxicology and Disease group, The Institute of Pharmaceutical Sciences (TIPS), 
      Tehran University of Medical Sciences, Tehran, Iran.
AD  - Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
FAU - Halvaei Khankahdani, Zahra
AU  - Halvaei Khankahdani Z
AD  - Faculty of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran.
FAU - Noruzi, Marzieh
AU  - Noruzi M
AD  - Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
FAU - Behmadi, Homayoon
AU  - Behmadi H
AD  - Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
FAU - Lavasani, Hoda
AU  - Lavasani H
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Rouini, Mohammad Reza
AU  - Rouini MR
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Sharifzadeh, Mohammad
AU  - Sharifzadeh M
AUID- ORCID: 0000-0001-9171-468X
AD  - Department of Neurosciences, School of Advanced Technologies in Medicine, Tehran 
      University of Medical Sciences, Tehran, Iran. msharifzadeh@sina.tums.ac.ir.
AD  - Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University 
      of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. 
      msharifzadeh@sina.tums.ac.ir.
LA  - eng
PT  - Journal Article
DEP - 20200227
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Reactive Oxygen Species)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Bucladesine/*administration & dosage
MH  - Hippocampus/*drug effects/metabolism
MH  - Male
MH  - Mitochondria/*drug effects/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Spatial Learning/*drug effects
MH  - Spatial Memory/*drug effects
OTO - NOTNLM
OT  - 3, 4- Methylenedioxymethamphetamine (MDMA)
OT  - ATP
OT  - Bucladesine
OT  - Cytochrome c
OT  - Learning and memory
OT  - Mitochondrial function
OT  - Oxidative stress
EDAT- 2020/02/28 06:00
MHDA- 2021/02/20 06:00
CRDT- 2020/02/28 06:00
PHST- 2019/11/13 00:00 [received]
PHST- 2020/02/14 00:00 [accepted]
PHST- 2020/02/07 00:00 [revised]
PHST- 2020/02/28 06:00 [pubmed]
PHST- 2021/02/20 06:00 [medline]
PHST- 2020/02/28 06:00 [entrez]
AID - 10.1007/s12640-020-00183-3 [pii]
AID - 10.1007/s12640-020-00183-3 [doi]
PST - ppublish
SO  - Neurotox Res. 2020 Jun;38(1):38-49. doi: 10.1007/s12640-020-00183-3. Epub 2020 
      Feb 27.