title: Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.
abstract: Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α2-adrenergic receptors.
authors.affiliation: Razi Drug Research Center & Pharmacology Department, School of Medicine, Iran University of Medical Sciences, Hemmat Highway, Beside Milad Tower, P.O. Box: 14496-14525, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Motaghinejad
authors.affiliation: Razi Drug Research Center & Pharmacology Department, School of Medicine, Iran University of Medical Sciences, Hemmat Highway, Beside Milad Tower, P.O. Box: 14496-14525, Tehran, Iran.
authors.forename: Manijeh
authors.initials: M
authors.lastname: Motevalian
authors.affiliation: Solid Dosage Form Department, Iran Hormone Pharmaceutical Company, 13185-1767, Tehran, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Shabab
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D000697:Central Nervous System Stimulants; D053583:Interleukin-1beta; D018341:Receptors, Adrenergic, alpha-2; D017470:Receptors, Glutamate; D014409:Tumor Necrosis Factor-alpha; D008774:Methylphenidate; D013482:Superoxide Dismutase
keywords: cerebral cortex; hippocampus; inflammation; methylphenidate; oxidative stress