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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.

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