PMID- 36571897
OWN - NLM
STAT- MEDLINE
DCOM- 20230207
LR  - 20230222
IS  - 1872-7123 (Electronic)
IS  - 0165-1781 (Linking)
VI  - 320
DP  - 2023 Feb
TI  - Repeated use of 3,4-methylenedioxymethamphetamine is associated with the 
      resilience in mice after chronic social defeat stress: A role of 
      gut-microbiota-brain axis.
PG  - 115020
LID - S0165-1781(22)00611-4 [pii]
LID - 10.1016/j.psychres.2022.115020 [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA), the most widely used illicit compound 
      worldwide, is the most attractive therapeutic drug for post-traumatic stress 
      disorder (PTSD). Recent observational studies of US adults demonstrated that 
      lifetime MDMA use was associated with lower risk of depression. Here, we examined 
      whether repeated administration of MDMA can affect resilience versus 
      susceptibility in mice exposed to chronic social defeat stress (CSDS). CSDS 
      produced splenomegaly, anhedonia-like phenotype, and higher plasma levels of 
      interleukin-6 (IL-6) in the saline-treated mice. In contrast, CSDS did not cause 
      these changes in the MDMA-treated mice. Analysis of gut microbiome found several 
      microbes altered between saline + CSDS group and MDMA + CSDS group. Untargeted 
      metabolomics analysis showed that plasma levels of N-epsilon-methyl-L-lysine in 
      the saline + CSDS group were significantly higher than those in the control and 
      MDMA + CSDS groups. Interestingly, there were positive correlations between 
      plasma IL-6 levels and the abundance of several microbes (or plasma 
      N-epsilon-methyl-L-lysine) in the three groups. Furthermore, there were also 
      positive correlations between the abundance of several microbes and 
      N-epsilon-methyl-L-lysine in the three groups. In conclusion, these data suggest 
      that repeated administration of MDMA might contribute to stress resilience in 
      mice subjected to CSDS through gut-microbiota-brain axis.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Qu, Youge
AU  - Qu Y
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Eguchi, Akifumi
AU  - Eguchi A
AD  - Department of Sustainable Health Science, Chiba University Center for Preventive 
      Medical Sciences, Chiba 263-8522, Japan.
FAU - Wan, Xiayun
AU  - Wan X
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Ma, Li
AU  - Ma L
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Chang, Lijia
AU  - Chang L
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Shan, Jiajing
AU  - Shan J
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Yang, Yong
AU  - Yang Y
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Mori, Chisato
AU  - Mori C
AD  - Department of Sustainable Health Science, Chiba University Center for Preventive 
      Medical Sciences, Chiba 263-8522, Japan; Department of Bioenvironmental Medicine, 
      Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
FAU - Hashimoto, Kenji
AU  - Hashimoto K
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221221
PL  - Ireland
TA  - Psychiatry Res
JT  - Psychiatry research
JID - 7911385
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - 0 (Interleukin-6)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Social Defeat
MH  - Interleukin-6
MH  - Lysine
MH  - Stress, Psychological/complications
MH  - *Gastrointestinal Microbiome
MH  - Brain
MH  - Mice, Inbred C57BL
OTO - NOTNLM
OT  - Anhedonia
OT  - Gut microbiota
OT  - MDMA
OT  - Resilience
OT  - Stress
OT  - Susceptibility
COIS- Declaration of Competing Interest Dr. Hashimoto is the inventor of filed patent 
      applications on "The use of R-ketamine in the treatment of psychiatric diseases", 
      "(S)-norketamine and salt thereof as pharmaceutical", "R-ketamine and derivative 
      thereof as prophylactic or therapeutic agent for neurodegeneration disease or 
      recognition function disorder", "Preventive or therapeutic agent and 
      pharmaceutical composition for inflammatory diseases or bone diseases", and 
      "R-ketamine and its derivatives as a preventive or therapeutic agent for a 
      neurodevelopmental disorder" by the Chiba University. Dr. Hashimoto has also 
      received speakers' honoraria, consultant fee, or research support from Abbott, 
      Boehringer-Ingelheim, Daiichi-Sankyo, Meiji Seika Pharma, Seikagaku Corporation, 
      Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm and Perception Neuroscience. 
      Other authors declare no conflict of interest.
EDAT- 2022/12/27 06:00
MHDA- 2023/02/08 06:00
CRDT- 2022/12/26 18:07
PHST- 2022/10/23 00:00 [received]
PHST- 2022/11/29 00:00 [revised]
PHST- 2022/12/20 00:00 [accepted]
PHST- 2022/12/27 06:00 [pubmed]
PHST- 2023/02/08 06:00 [medline]
PHST- 2022/12/26 18:07 [entrez]
AID - S0165-1781(22)00611-4 [pii]
AID - 10.1016/j.psychres.2022.115020 [doi]
PST - ppublish
SO  - Psychiatry Res. 2023 Feb;320:115020. doi: 10.1016/j.psychres.2022.115020. Epub 
      2022 Dec 21.