title: The neuroprotective effect of lithium against high dose methylphenidate: Possible role of BDNF.
abstract: Methylphenidate (MPH) is a neural stimulant with unclear neurochemical and behavioral effects. Lithium is a neuroprotective agent in use clinically for the management of manic-depressive and other neurodegenerative disorders. This study investigated the protective effect of lithium on MPH-induced oxidative stress, anxiety, depression and cognition impairment. Forty-eight adult male rats were divided randomly and equally into 6 groups. Treatment groups were received MPH (10mg/kg) and various doses of lithium (75, 150 and 300mg/kg) simultaneously and also lithium (150mg/kg) alone for 21 days. Elevated Plus Maze and Forced Swim Test were used to determine the level of anxiety and depression in animals. Morris Water Maze was used to evaluate spatial learning and memory. The hippocampi of rats were isolated and the level and activity of oxidative, anti-oxidant and inflammatory factors were measured. Also brain derived neurotropic factor expression level was measured by RT-PCR and western blotting. MPH (10mg/kg) caused behaviors indicative of anxiety and depression-like phenotypes in EPM and FST and cognition impairment in MWM. While lithium in all mentioned doses inhibited these effects. Treatment with MPH significantly increased lipid peroxidation, mitochondrial GSH content and IL-1β and TNF-α levels in isolated hippocampal cells. Moreover superoxide dismutase and glutathione peroxidase activities and BDNF expression remarkably decreased. Various doses of lithium attenuated these effects and significantly mitigated MPH-induced oxidative damage, inflammation and increased BDNF expression level. Lithium has the potential to act as a neuroprotective agent against MPH induced toxicity in rat brain and this might be mediated by BDNF expression in hippocampus of 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.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Seyedjavadein
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: Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Asadi
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000633:toxicity*; D019964:Mood Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D016207:Cytokines; D018020:Lithium Compounds; D018696:Neuroprotective Agents; D008774:Methylphenidate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Anti-oxidant; Anxiety; BDNF; Cognition impairment; Depression; Inflammatory factors; Lithium; Methylphenidate; Neurodegeneration