title: Bupropion attenuates kainic acid-induced seizures and neuronal cell death in rat hippocampus.
abstract: Excessive release of glutamate is believed to be a major component of cell damage following excitotoxicity associated with epilepsy. Bupropion, an atypical antidepressant, has been shown to inhibit glutamate release from rat cerebrocortical nerve terminals. The present study was undertaken to investigate whether bupropion has anti-seizure and anti-excitotoxic effects by using a kainic acid (KA) rat seizure model, an animal model for temporal lobe epilepsy and excitotoxic neurodegeneration. Our results show that bupropion (10 or 50mg/kg), administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg) intraperitoneal injection, increased the seizure latency and decreased the seizure score. Bupropion pretreatment attenuated KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. Furthermore, KA-induced c-Fos expression and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in the hippocampus were also reduced by bupropion pretreatment. These results suggest that bupropion has therapeutic potential in the treatment of seizure and other neurological diseases associated with excitotoxicity.
authors.affiliation: Department of Neurology, Chi Mei Medical Center, Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Kao-Chang
authors.initials: KC
authors.lastname: Lin
authors.forename: Chia-Chuan
authors.initials: CC
authors.lastname: Wang
authors.forename: Su-Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D016642:Bupropion / Q000494:pharmacology* / Q000627:therapeutic use; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D000927:Anticonvulsants; D016760:Proto-Oncogene Proteins c-fos; D016642:Bupropion; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D007608:Kainic Acid
keywords: Bupropion; ERK1/2; Excitotoxicity; Hippocampus; JNK; KA; Kainic acid; MAPKs; Neuroprotection; PBS; Seizure; TBS; Tris-buffered saline; c-Jun N-terminal kinase; extracellular signal-regulated kinase; i.p.; intraperitoneal; kainic acid; mitogen-activated protein kinases; phosphate-buffered saline