MDMA appears to confer resilience in a rodent model of chronic social defeat stress

A new experiment in Japan has shown that when mice are exposed to a chronic stress condition of social defeat, they develop a number of adverse health conditions. But these adverse health conditions were absent in mice that were repeatedly injected with MDMA (3,4-Methylenedioxymethamphetamine), also known as club drug ecstasy. The study was published in Psychiatry research.

MDMA is one of the most widely used recreational drugs in the world. It produces prosocial feelings and increases empathy and sociability. However, it is also known to produce hallucinogenic effects and to facilitate a host of adverse mental health consequences for prolonged use. First created in Germany for the purpose of researching a possible appetite suppressant, it is now banned in most of the world.

On the other hand, a great recent study of American adults found that ecstasy use was associated with reduced likelihood of psychological distress and suicidal thoughts. Another study that was conducted between 2015-2020 and included more than 200,000 American adults linked the use of ecstasy with a decreased likelihood of serious psychological distress, depression and suicidal thoughts. This was in contrast to the use of the hallucinogenic drug LSD (lysergic acid diethylamide), which was linked to an increased likelihood of depression and suicidal thoughts in the same study.

Recent studies have also brought into focus the potential use of MDMA as a treatment for post-traumatic stress disorder (PTSD). A to study reported that ecstasy could produce a significant reduction in symptom intensity in patients with severe post-traumatic stress disorder compared to placebo. In their new study, lead researcher Youge Qu and his colleagues wanted to examine whether repeatedly giving MDMA to mice helped them become resistant to the effects of chronic social defeat stress.

Chronic social defeat stress (CSDS) is a protocol (scientific procedure) in which a mouse is exposed to a larger aggressive mouse in an enclosed space. This is followed by a confrontation between the two mice in which the mouse subjected to this treatment is defeated and forced into a subordinate position (social defeat).

Typically, this procedure is repeated every day for 10 days. The chronic social defeat protocol of stress is known to produce depression-like effects in mice exposed to it with a number of easily detectable effects, such as increased spleen weight and lower preference for sucrose. That is why it is widely used in research on mice.

This study was carried out on 7-week-old mice, while 13-week-old mice (therefore older) were used as aggressors. Mice had water and food available at all times. They were divided into three groups. The first group was a control. She was given a saline solution (instead of MDMA) and was not exposed to the chronic stress of social defeat. The second group was exposed to chronic social defeat stress for 10 days, every day using a larger aggressor mouse and given a saline solution. The third group was subjected to the chronic social defeat protocol and given MDMA.

At specific points, the researchers assessed whether the mice lost the ability to feel pleasure (anhedonia) using a sucrose preference test (one of the expected effects of chronic social defeat stress treatment). They also collected blood from his heart at the end of the treatment, stool samples to analyze the composition of the microorganisms in his intestines, and measured the levels of several compounds that are known to be indicators of adverse effects of the protocol of chronic stress of social defeat.

Mice that were exposed to the chronic social defeat protocol, but received a saline injection instead of MDMA, had increased spleen weight, which is one of the known adverse consequences of this protocol. These mice also had a reduced preference for sucrose, indicating anhedonia. Levels of other indicators of adverse effects of chronic social defeat stress protocols were all elevated in mice that were injected with a saline solution. All these adverse changes were absent in mice receiving MDMA injections.

In addition, the researchers found changes in the composition of intestinal microbes in mice that were subjected to the chronic social defeat stress protocol and injected with the saline protocol. These changes were absent in mice that underwent the same protocol, but were injected with MDMA. The researchers attributed these changes to the axis called gut-microbiota-brain, a mechanism of chemical pathways that allow the interaction between brain activity and microorganisms in the gut.

“The present study suggests that repeated use of MDMA could be associated with resilience in mice subjected to CSDS through the gut-microbiota-brain axis. It is likely that abnormalities in the gut-microbiota-brain axis including metabolites derived from microbes can contribute to susceptibility to stress-related disorders. Finally, MDMA would be a prophylactic and therapeutic drug to prevent the onset of stress-related disorders,” the researchers concluded.

The study sheds light on the biochemical mechanisms of stress. However, it also has limitations that must be considered. In particular, the study did not provide evidence supporting the role of the gut-microbiota-brain axis in the development of stress resistance in mice that received MDMA. In addition, it remains unknown if the mechanism through which the effects of MDMA were obtained in mice can be reproduced in humans and if they can, if they will be desirable.

The observed effect could also be drug-induced indifference to social situations rather than resilience. The indifference and neglect of social situations (such as employment, family obligations, financial responsibilities and other social responsibilities) in the man who consumes drugs is generally seen as an undesirable effect of l ‘use of drugs even if it saves the person from the effects of stress that these. situations can cause.

The paper, “Repeated use of 3,4-methylenedioxymethamphetamine is associated with resilience in mice after chronic social defeat stress: a role of the gut-microbiota-brain axis“, was written by Youge Qu, Akifumi Eguchi, Xiayun Wan, Li Ma, Lijia Chang, Jiajing Shan, Yong Yang, Chisato Mori, and Kenji Hashimoto.

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