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 DOI: 10.21203/rs.3.rs-420208/v1 (opens in new tab)
Summary
AI-generated from the abstractIn rats, the recreational drug MDMA (Ecstasy) impairs spatial memory and increases oxidative stress and cell death in the hippocampus. Atorvastatin (5, 10, 20 mg/kg) and rosuvastatin (20 mg/kg), given orally for 21 days, prevented these memory deficits and reduced the MDMA-induced rise in reactive oxygen species, lipid peroxidation, and caspase-3 and -9 activities. The results suggest that these statins protect against MDMA neurotoxicity by suppressing oxidative stress and apoptosis.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Adult male Wistar rats |
| Interventions | Atorvastatin Rosuvastatin |
| Dose | 5, 10, 20 mg/kg orally for atorvastatin; 5, 10, 20 mg/kg orally for rosuvastatin |
| Duration | 21 consecutive days of statin administration; MDMA injected 30 min before training sessions over 4 training days |
| Key finding | 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.