Involvement of AMPA/kainate and GABAA receptors in topiramate neuroprotective effects against methylphenidate abuse sequels involving oxidative stress and inflammation in rat isolated hippocampus.
Abuses of methylphenidate (MPH) as psychostimulant cause neural damage of brain cells. Neuroprotective properties of topiramate (TPM) have been indicated in several studies but its exact mechanism of action remains unclear. The current study evaluates protective role of various doses of TPM and its mechanism of action in MPH induced oxidative stress and inflammation. The neuroprotective effects of various doses of TPM against MPH induced oxidative stress and inflammation were evaluated and then the action of TPM was studied in presence of domoic acid (DOM), as AMPA/kainate receptor agonist and bicuculline (BIC) as GABAA receptor antagonist, in isolated rat hippocampus. Open Field Test (OFT) was used to investigate motor activity changes. Oxidative, antioxidant and inflammatory factors were measured in isolated hippocampus. TPM (70 and 100mg/kg) decreased MPH induced motor activity disturbances and inhibit MPH induced oxidative stress and inflammation. On the other hand pretreatment of animals with DOM or BIC, inhibit this effect of TPM and potentiate MPH induced motor activity disturbances and increased lipid peroxidation, mitochondrial oxidized form of glutathione (GSSG) level, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in isolated hippocampal cells and decreased reduced form of glutathione (GSH) level, superoxide dismutase, glutathione peroxidase and glutathione reductase activity. It seems that TPM can protect cells of hippocampus from oxidative stress and neuroinflammation and it could be partly by activation of GABAA receptor and inhibition of AMPA/kainite receptor.
Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: dr.motaghinejad6@gmail.com.
Majid
M
Motaghinejad
Razi Drug Research Center & Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: motevalian.m@iums.ac.ir.
Manijeh
M
Motevalian
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019803:Glutathione Disulfide / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D058446:Ligand-Gated Ion Channels / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000077236:Topiramate
D005632:Fructose; D019803:Glutathione Disulfide; D058446:Ligand-Gated Ion Channels; D008774:Methylphenidate; D018696:Neuroprotective Agents; D010088:Oxidoreductases; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D013482:Superoxide Dismutase; D000077236:Topiramate; C020667:glutathione oxidase
Methylphenidate; Oxidative stress and inflammation; Topiramate