Protective Effects of Atorvastatin and Rosuvastatin on 3,4-methylenedioxymethamphetamine (MDMA)-Induced Spatial Learning and Memory Impairment
Majid Eslami, Laleh Khorshidi, Maryam Ghasemi, Amir Rashidian, Mahdi Mirghazanfari, Akram Nezhadi, Mohsen Chamanara, Ruhollah Mirjani
Research Square preprint DOI: 10.21203/rs.3.rs-420208/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study |
|---|---|
| Population | Adult male Wistar rats |
| Interventions | Atorvastatin Rosuvastatin MDMA |
| Dose | Atorvastatin 5, 10, 20 mg/kg; rosuvastatin 5, 10, 20 mg/kg; MDMA 2.5, 5, 10 mg/kg |
| Duration | 21 consecutive days of statin administration; MDMA injected 30 min before training sessions over 4 training days |
| Measures | Morris water maze (MWM), reactive oxygen species (ROS) production, lipid peroxidation (LPO), caspase-3 activity, caspase-9 activity |
| Topics | MDMA |
| Key points | Atorvastatin and rosuvastatin ameliorated MDMA-induced spatial memory impairment and hippocampal apoptosis by suppressing reactive oxygen species production, lipid peroxidation, and caspase-3 and -9 activities. |
Abstract
Abstract 3,4‐methylenedioxymethamphetamine (MDMA) or "Ecstasy", which has been used for recreational purposes, is shown to cause learning and memory impairment. Statins, beyond their efficient cholesterol-lowering action through inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-COA) reductase, possess multiple neuroprotective impacts referred to as pleiotropic effects. In this regard, we aimed to investigate the protective effect of atorvastatin and rosuvastatin in MDMA-induced neurotoxicity. Adult male Wistar rats received atorvastatin (5, 10, 20 mg/kg; orally) and rosuvastatin (5, 10, 20 mg/kg; orally) for 21 consecutive days. Then, Morris water maze (MWM) was performed to examine learning and memory functions. Rats were injected with MDMA (2.5, 5, and 10 mg/kg; I.P) 30 min before training sessions in 4 training days of MWM task. Afterward, rats were sacrificed under general anesthesia and their hippocampuses were dissected to evaluate reactive oxygen species (ROS) production, lipid peroxidation (LPO), and caspase-3 and -9 activities. Our Findings showed that MDMA impaired spatial memory functions and dramatically upregulated ROS production, LPO, and caspase-3 and 9 activities. Also, atorvastatin (5, 10, 20 mg/kg) and rosuvastatin (20 mg/kg) significantly improved memory performances and inhibited upregulation of ROS, LPO, and caspase-3 and -9 activities induced by MDMA. In conclusion, the amelioration of MDMA-induced memory impairment and hippocampal apoptosis through atorvastatin and rosuvastatin could be accredited to the observed suppression of ROS production, LPO, and caspase-3 and -9 activities, since excessive exposure of hippocampus to oxidative stress enhanced apoptotic caspases activities, promoted to neuronal apoptosis.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 11
- Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Journal of Neurology, Neurosurgery, and Psychiatry June 1, 2000
- Patterns of simultaneous polysubstance use in drug using university students Human Psychopharmacology: Clinical and Experimental June 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
- Role of hyperthermia in the protective action of clomethiazole against MDMA (‘ecstasy’)‐induced neurodegeneration, comparison with the novel NMDA channel blocker AR‐R15896AR British Journal of Pharmacology June 1, 1998
- Pro‐oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes British Journal of Pharmacology April 21, 2011
and 6 more in the library