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
Summary
MDMA causes learning and memory impairment in male Wistar rats, increasing reactive oxygen species production and apoptosis markers. However, atorvastatin and rosuvastatin significantly improved memory performance and reduced these harmful effects when administered at various doses over 21 days. The protective effects are linked to the suppression of oxidative stress and apoptosis in the hippocampus.
Study at a glance
| Population | adult male Wistar rats |
|---|---|
| Key finding | Atorvastatin and rosuvastatin significantly improved memory performances and inhibited the upregulation of oxidative stress and apoptosis markers induced by MDMA. |
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.