title: Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats.
abstract: Methylphenidate (MPH) is a central stimulant, prescribed for the treatment of attention deficit/hyperactivity disorder. The long-term behavioral consequences of MPH treatment are unknown. In this study, the oxidative stress and neuroinflammation induced by various doses of MPH were investigated. Forty adult male rats were divided into 5 groups; and treated with different doses of MPH for 21 days. Twenty four hours after drug treatment, Open Field Test (OFT) was performed in all animals. At the end of the study, blood cortisol level (BCL) was measured and hippocampus was isolated and oxidative stress and inflammation parameters and histological changes were analyzed. Chronic MPH at all doses decreased central square entries, number of rearing, ambulation distance and time spent in central square in OFT. BCL increased in doses 10 and 20mg/kg of MPH. Furthermore, MPH in all doses markedly increased lipid peroxidation, mitochondrial oxidized glutathione (GSSG) level, Interleukin 1β (IL-1β) and Tumor Necrosis Factor α (TNF-α) in isolated hippocampus. MPH (10 and 20mg/kg) treated groups had decreased mitochondrial reduced glutathione (GSH) content, and reduced superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) activities. 10 and 20mg/kg of MPH change cell density and morphology of cells in Dentate Gyrus (DG) and CA1 areas of hippocampus. Chronic treatment with high doses of MPH can cause oxidative stress, neuroinflammation and neurodegeneration in hippocampus of adult rats.
authors.affiliation: Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Motaghinejad
authors.affiliation: Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: Motevalian.m@iums.ac.ir.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Motevalian
authors.affiliation: Solid Dosage Form Department, Iran Hormone Pharmaceutical Company, Tehran, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Shabab
mesh_terms: D000818:Animals; D002452:Cell Count; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006854:Hydrocortisone / Q000097:blood; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008774:Methylphenidate / Q000633:toxicity*; D008928:Mitochondria / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D008774:Methylphenidate; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D006854:Hydrocortisone
keywords: Hippocampus; Inflammation; Methylphenidate; Oxidative stress