3,4-methylenedioxymethamphetamine (MDMA) or "Ecstasy", which has been used for recreational purposes, is shown to cause learning and memory impairment. Statins, beyond their e cient cholesterollowering 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 sacri ced 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) signi cantly 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.

A natural compound of marine herbal origin has been used in Persian Traditional Medicine to relieve some symptoms of multiple sclerosis. The present study investigated the anti-inflammatory effects of a patented extracts of the traditional receipt (MS14). In this preliminary experiment, we used seven groups of six rats: the control group received vehicle, the two positive control groups were treated with either sodium salicylate (300 mg/kg) intraperitoneal (i.p.) or methyl prednisolon (MPN 10 mg/kg) i.p., while the test groups were treated with a solution centrifuged MS14 (SANT 100 mg/kg) and suspension of MS14 (SUSP 100, 150, 300 mg/kg) i.p. After thirty minutes, paw volume was measured by plethysmometer and immediately formalin solution was injected subcutaneously into the hind paw and after an hour, inflamed paw volume was measured. In days 2-8, the inflamed paw volume was measured and immediately drugs were injected i.p. The anti-inflammatory effect of MPN was significant only on days 5 and 6. The anti-inflammatory effect of SS was significant only on the 6th day, while the anti-inflammatory effect of SANT MS14 (100 mg/kg) was also significant only on the 6th day. SUSP MS14 (150 mg/kg) significantly reduced edema from second to 6th day. Intra-peritoneal injection of SUSP MS14 with 300 mg/kg was toxic, so excluded from the study. This research indicates that the MS14 possesses an anti-inflammatory effect after intra-peritoneal administration. Comparative anti-inflammatory effects of MS14 with Glucocorticoids in this study, may justify a possible mechanism for its action in multiple sclerosis, if further studies will provid strong statistically confirmatory effects in animals and safety human trials.

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.