Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.
Ghorban Taghizadeh, Jalal Pourahmad, Hajar Mehdizadeh, Alireza Foroumadi, Anahita Torkaman-Boutorabi, Shokoufeh Hassani, Parvaneh Naserzadeh, Reyhaneh Shariatmadari, Mahdi Gholami, Mohammad-Reza Rouini, Mohammad Sharifzadeh
Free radical biology & medicine October 2016 DOI: 10.1016/j.freeradbiomed.2016.07.018 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Male Wistar rats |
| Interventions | MDMA Treadmill exercise |
| Dose | 5, 10, and 15 mg/kg MDMA |
| Duration | 2-week or 4-week exercise; MDMA injected 30 min before the first training trial on 4 training days of the Morris water maze |
| Measures | Morris water maze (MWM), reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outer membrane damage, cytochrome c release, ADP/ATP ratio |
| Topics | MDMA |
| Keywords | 3, 4-Methylenedioxymethamphetamine MDMA Cytochrome c Learning and memory Mitochondria Oxidative stress Physical exercise Ros |
| Key findings | MDMA impaired spatial learning and memory in a dose-dependent manner and disrupted brain mitochondrial function, increasing ROS, collapsing mitochondrial membrane potential, causing swelling and outer membrane damage, releasing cytochrome c, and raising the ADP/ATP ratio. Short-term (2-week) and long-term (4-week) treadmill exercise reduced these MDMA-induced cognitive and mitochondrial impairments, suggesting exercise may protect brain mitochondria against MDMA neurotoxicity. |
Abstract
Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 9
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- Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats International Journal of Molecular Sciences March 12, 2019
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- A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA) Current Research in Toxicology May 27, 2022
- The combination of exercise and psychedelics for the treatment of major depressive disorder Discover Mental Health March 7, 2026
and 4 more in the library
Cites 12
- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective Journal of Psychopharmacology March 1, 2006
- 3,4-Methylenedioxymethamphetamine (Ecstasy)-Induced Learning and Memory Impairments Depend on the Age of Exposure during Early Development Journal of Neuroscience May 1, 2001
- Pro‐oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes British Journal of Pharmacology April 21, 2011
- Protective effects of N-acetylcysteine on 3, 4-methylenedioxymethamphetamine-induced neurotoxicity in male Sprague-Dawley rats. Metabolic Brain Disease December 2013
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