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. (February 2023)

• Record Type: Journal Article
• Authors: Qu, Youge; Eguchi, Akifumi; Wan, Xiayun; Ma, Li; Chang, Lijia; Shan, Jiajing; Yang, Yong; Mori, Chisato; Hashimoto, Kenji
• Is Part Of: Psychiatry research. Volume 320(2023)
• Publication Date: 2023-02
• Subjects: Anhedonia -- Gut microbiota -- MDMA -- Susceptibility -- Stress -- Resilience; CSDS chronic social defeat stress -- FDR false discovery rate -- IL-6 interleukin-6 -- MDMA 3, 4-methylenedioxymethamphetamine -- PTSD post-traumatic stress disorder; Psychiatry -- Periodicals; Psychiatry -- periodicals; Psychiatrie -- Périodiques; 616.89
• DOI: 10.1016/j.psychres.2022.115020
• Languages: English
• ISSNs: 0165-1781

Abstract

Highlights: Lifetime MDMA use in US adults was associated with lower risk of depression. Treatment with MDMA was associated with stress resilience in mice after stress. Abnormalities in gut microbiota and metabolites may play a role in MDMA-induced resilience. MDMA may contribute to stress resilience through gut–microbiota–brain axis. MDMA would be a prophylactic or therapeutic drug for stress-related disorders. Abstract: 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.