Rehabilitation Research Center, Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran.
Department of Neurosciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Arch Toxicol. 2020 Mar;94(3):911-925. doi: 10.1007/s00204-020-02673-x. Epub 2020 Feb 18.
MDMA-induced impairments of memory performance have been reported in different human and animal studies. However, the correlation between spatial memory impairment, brain mitochondrial function, and concentrations of MDMA and its metabolites has not yet been investigated despite it being needed for comparison with human studies. Therefore, the aim of this study was to investigate the dose concentration and spatial memory as well as brain mitochondrial function association after MDMA administration in rats. We assessed the effects of MDMA [0.5, 2.5, 5, 10 and 15 mg/kg; intraperitoneally (I.P)] on spatial memory of male Wistar rats in the Morris water maze test (MWM) and brain mitochondrial function (i.e., reactive oxygen species, mitochondrial membrane potential, swelling and outer membrane damage, cytochrome c release, and ADP/ATP ratio). Concentrations of MDMA and its metabolite, MDA, were determined in plasma, cerebrospinal fluid (CSF) and brain which was obtained immediately after probe test of MWM (i.e., 4 h after last training trial). The results of this study indicate nonlinear kinetics of MDMA after I.P adminstration. Also, an insignificant correlation was observed between MDMA doses and the MDA/MDMA ratio in plasma, CSF, and brain. Moreover, the results showed that MDMA, but not MDA, accumulated in brain tissue by increasing the administered doses. Beside, MDMA-induced impairments of spatial memory and brain mitochondrial function were significantly correlated with the concentrations of both MDMA and MDA in plasma, CSF, and brain. Therefore, it can be suggested that MDMA and its metabolite, MDA, affect spatial memory and brain mitochondrial function.
在不同的人体和动物研究中已经报道了 MDMA 引起的记忆表现受损。然而，尽管需要与人体研究进行比较，但空间记忆损伤、大脑线粒体功能以及 MDMA 和其代谢物浓度之间的相关性尚未得到研究。因此，本研究的目的是研究 MDMA 给药后大鼠的剂量浓度、空间记忆和大脑线粒体功能的关联。我们评估了 MDMA[0.5、2.5、5、10 和 15mg/kg；腹腔内（I.P）]对雄性 Wistar 大鼠在 Morris 水迷宫测试（MWM）中的空间记忆和大脑线粒体功能（即活性氧、线粒体膜电位、肿胀和外膜损伤、细胞色素 c 释放和 ADP/ATP 比）的影响。MDMA 和其代谢物 MDA 的浓度在血浆、脑脊液（CSF）和大脑中进行了测定，这些样本是在 MWM 的探针测试后立即获得的（即在最后一次训练试验后 4 小时）。本研究的结果表明 MDMA 在 I.P 给药后呈现非线性动力学。此外，在血浆、CSF 和大脑中，MDMA 剂量与 MDA/MDMA 比值之间观察到无显著相关性。此外，结果表明，MDMA 而不是 MDA，通过增加给药剂量而在脑组织中积累。此外，MDMA 引起的空间记忆和大脑线粒体功能损伤与血浆、CSF 和大脑中 MDMA 和 MDA 的浓度显著相关。因此，可以认为 MDMA 和其代谢物 MDA 影响空间记忆和大脑线粒体功能。
