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.
Youge Qu, Akifumi Eguchi, Xiayun Wan, Li Ma, Lijia Chang, Jiajing Shan, Yong Yang, Chisato Mori, Kenji Hashimoto
Psychiatry Research December 21, 2022 DOI: 10.1016/j.psychres.2022.115020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Mice exposed to chronic social defeat stress |
| Intervention | MDMA |
| Topics | MDMA |
| Keywords | Brain Animals Mice, inbred c57bl N-methyl-3,4-methylenedioxyamphetamine Lysine Interleukin-6 Stress, psychological Gastrointestinal microbiome Social defeat Susceptibility Resilience Gut microbiota Anhedonia |
| Key findings | Repeated MDMA administration prevented splenomegaly, anhedonia-like behavior, and elevated plasma IL-6 in mice exposed to chronic social defeat stress, whereas saline-treated stressed mice showed these changes. The authors suggest MDMA may contribute to stress resilience through the gut-microbiota-brain axis, citing altered gut microbes and higher plasma N-epsilon-methyl-L-lysine in the saline-stressed group. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- A role of gut-brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress. Pharmacology, Biochemistry, and Behavior May 1, 2024
- Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice. European Journal of Pharmacology March 15, 2025
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