Simvastatin Neuroprotective Properties against Methylphenidate-Induced Neurodegeneration: Histological and Behavioral Evidence

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Background: The present study investigated the neuroprotective effect of simvastatin (SIM) against behavioral changes and histological alterations in the hippocampus induced by methylphenidate (MPH). Materials and Methods: Male Wistar rats were divided into the following groups: control, normal saline (0.2 mL), MPH (10 mg/kg), and MPH (10 mg/kg) plus SIM (10, 20, or 40 mg/kg). Open Field Test (OFT) and Elevated Plus Maze (EPM) evaluated mood and motor activity. Hippocampus DG and CA1 histomorphological changes were also evaluated. Result: MPH caused anxiety, depression, and motor activity disorder in animals in OFT and EPM ( P < 0.001), while SIM altered MPH-induced mood and motor activity disorders in both tests ( P < 0.001). MPH caused quantitative ( P < 0.001) and qualitative changes in hippocampus DG and CA1 cells. SIM (10, 20, and 40 mg/kg) inhibited these neurodegenerative changes of MPH on DG and CA1 cell counts ( P < 0.001) and morphology. Conclusion: SIM conferred neuroprotective properties against MPH-induced behavioral and inhibited MPH-prompted hippocampal cell changes.