MDMA (3,4-Methylenedioxymethamphetamine) is a common recreational drug of abuse which causes neurodegeneration. Nicotine and modafinil provide antioxidant and neuroprotective properties and may be beneficial in the management of MDMA-induced neurotoxicity. The purpose of this study was to characterize how acute and chronic administration of nicotine and/or modafinil exert protective effects against the MDMA-induced impaired cognitive performance, oxidative stress, and neuronal loss. Adult male rats were divided into three groups, namely control, MDMA and treatment (modafinil and/or nicotine). MDMA (10 mg/kg) was administered intraperitoneally during a three-week schedule (two times/day for two consecutive days/week). The treated-groups were classified based on the acute or chronic status of treatment. In the groups which underwent acute treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected just prior to the MDMA administration (acute nicotine (NA), acute modafinil (MA), and acute nicotine and modafinil (NMA)). In the rats which received chronic treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected every day during the three week-schedule administration of MDMA (chronic nicotine (NC), chronic modafinil (MC), and chronic nicotine and modafinil (NMC)). Learning and memory performance, as well as avoidance response, were assessed by Morris water maze and Shuttle box, respectively. Our findings indicate enhanced learning and memory and avoidance response in the NMC group. By TUNEL test and Cresyl Violet staining we evaluated neuronal loss and apoptosis in the hippocampal CA1 and found increased neuronal viability in the NMC group. On the other hand, chronic administration of modafinil and nicotine significantly down-regulated the caspase 3 and up-regulated both BDNF and TrkB levels in the MDMA-received rats. The serum levels of glutathione peroxidase (GPx) and total antioxidant capacity (TAC) were evaluated and we found that the alterations of serum levels of GPx and TAC were considerably prevented in the NMC group. The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA.

MDMA（3,4-亚甲二氧基甲基苯丙胺）是一种常见的娱乐性滥用药物，会导致神经退化。尼古丁和莫达非尼提供抗氧化和神经保护特性，可能有益于管理 MDMA 引起的神经毒性。本研究的目的是描述尼古丁和/或莫达非尼的急性和慢性给药如何对 MDMA 引起的认知能力受损、氧化应激和神经元损失发挥保护作用。成年雄性大鼠分为三组，即对照组、MDMA和治疗组（莫达非尼和/或尼古丁）。MDMA (10 mg/kg) 在为期三周的计划中腹膜内给药（两次/天，连续两天/周）。根据治疗的急性或慢性状态对治疗组进行分类。在接受急性治疗的组中，尼古丁 (0.5 mg/kg) 和/或莫达非尼 (100 mg/kg) 在 MDMA 给药前注射（急性尼古丁 (NA)、急性莫达非尼 (MA) 和急性尼古丁和莫达非尼 (NMA)）。在接受慢性治疗的大鼠中，在三周的 MDMA（慢性尼古丁 (NC)、慢性莫达非尼 (MC)和慢性尼古丁和莫达非尼 (NMC))。学习和记忆表现，以及回避反应，分别通过莫里斯水迷宫和穿梭箱进行评估。我们的研究结果表明 NMC 组的学习和记忆以及回避反应增强。通过 TUNEL 测试和甲酚紫染色，我们评估了海马 CA1 中的神经元损失和细胞凋亡，发现 NMC 组的神经元活力增加。另一方面，在接受 MDMA 的大鼠中，长期服用莫达非尼和尼古丁显着下调 caspase 3 并上调 BDNF 和 TrkB 水平。评估了谷胱甘肽过氧化物酶 (GPx) 和总抗氧化能力 (TAC) 的血清水平，我们发现 NMC 组的血清 GPx 和 TAC 水平的改变得到了显着抑制。总体结果表明，尼古丁和莫达非尼共同给药可将大脑从 MDMA 诱导的神经毒性中拯救出来。我们建议尼古丁和莫达非尼联合治疗可被视为一种可能的治疗方法，以减少由 MDMA 引起的神经系统疾病。评估了谷胱甘肽过氧化物酶 (GPx) 和总抗氧化能力 (TAC) 的血清水平，我们发现 NMC 组的血清 GPx 和 TAC 水平的改变得到了显着抑制。总体结果表明，尼古丁和莫达非尼共同给药可将大脑从 MDMA 诱导的神经毒性中拯救出来。我们建议尼古丁和莫达非尼联合治疗可被视为一种可能的治疗方法，以减少由 MDMA 引起的神经系统疾病。评估了谷胱甘肽过氧化物酶 (GPx) 和总抗氧化能力 (TAC) 的血清水平，我们发现 NMC 组的血清 GPx 和 TAC 水平的改变得到了显着抑制。总体结果表明，尼古丁和莫达非尼共同给药可将大脑从 MDMA 诱导的神经毒性中拯救出来。我们建议尼古丁和莫达非尼联合治疗可被视为一种可能的治疗方法，以减少由 MDMA 引起的神经系统疾病。