title: The anti-inflammatory activity of duloxetine, a serotonin/norepinephrine reuptake inhibitor, prevents kainic acid-induced hippocampal neuronal death in mice.
abstract: Duloxetine (DXT), a potent serotonin/norepinephrine reuptake inhibitor, is widely used in the treatment of major depressive disorder. In the present study, we examined the effects of DXT treatment on seizure behavior and excitotoxic neuronal damage in the mouse hippocampal CA3 region following intraperitoneal kainic acid (KA) injection. DXT treatment showed no effect on KA-induced behavioral seizure activity. However, treatment with 10mg/kg DXT reduced KA-induced neuronal death in the hippocampal CA3 region at 72h after KA administration, and treatment with 20 and 40mg/kg DXT showed a noticeable neuroprotection in the hippocampal CA3 region after KA injection. In addition, KA-induced activations of microglia and astrocytes as well as KA-induced increases of TNF-α and IL-1β levels were also suppressed by DXT treatment. These results indicate that DXT displays the neuroprotective effect against KA-induced excitotoxic neuronal death through anti-inflammatory action.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, South Korea.
authors.forename: Hee-Soo
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Surgery, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Seongkweon
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Emergency Medicine and Institute of Medical Sciences, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, South Korea. Electronic address: anaphy@dankook.ac.kr.
authors.forename: Choong-Hyun
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D056654:CA3 Region, Hippocampal / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity*; D053583:Interleukin-1beta / Q000187:drug effects*; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects*; D000066829:Neuroprotection / Q000187:drug effects*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*
chemical_list: D018690:Excitatory Amino Acid Agonists; D053583:Interleukin-1beta; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D014409:Tumor Necrosis Factor-alpha; D000068736:Duloxetine Hydrochloride; D007608:Kainic Acid
keywords: Astrocytes; Excitotoxic neuronal damage; Microglia; Pro-inflammatory cytokines; Seizure; Serotonin/norepinephrine reuptake inhibitor