Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats.
Golshad Kowsari, Soraya Mehrabi, Sara Soleimani Asl, Mahsa Pourhamzeh, Kazem Mousavizadeh, Mehdi Mehdizadeh
Journal of chemical neuroanatomy October 2021 DOI: 10.1016/j.jchemneu.2021.101986 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Adult male rats |
| Interventions | MDMA Nicotine Modafinil |
| Dose | MDMA 10 mg/kg; nicotine 0.5 mg/kg; modafinil 100 mg/kg |
| Duration | Three-week schedule (MDMA two times/day for two consecutive days/week) |
| Measures | Morris water maze, Shuttle box, TUNEL test, Cresyl Violet staining, caspase 3, BDNF, TrkB, glutathione peroxidase (GPx), total antioxidant capacity (TAC) |
| Topics | MDMA |
| Keywords | Apoptosis Modafinil Nicotine Oxidative stress |
| Key findings | Chronic co-administration of nicotine and modafinil in MDMA-treated rats improved learning, memory, and avoidance responses, increased neuronal viability in hippocampal CA1, down-regulated caspase 3, up-regulated BDNF and TrkB, and prevented changes in serum GPx and TAC. The authors suggest this combination could be considered a possible treatment for MDMA-induced neurotoxicity. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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and 13 more in the library