The anti-inflammatory activity of duloxetine, a serotonin/norepinephrine reuptake inhibitor, prevents kainic acid-induced hippocampal neuronal death in mice

Hee-Soo Choi; Joon Ha Park; Ji Hyeon Ahn; Seongkweon Hong; Jun Hwi Cho; Moo-Ho Won; Choong-Hyun Lee

doi:10.1016/j.jns.2015.10.001

The anti-inflammatory activity of duloxetine, a serotonin/norepinephrine reuptake inhibitor, prevents kainic acid-induced hippocampal neuronal death in mice

J Neurol Sci. 2015 Nov 15;358(1-2):390-7. doi: 10.1016/j.jns.2015.10.001. Epub 2015 Oct 3.

Authors

Hee-Soo Choi¹, Joon Ha Park², Ji Hyeon Ahn², Seongkweon Hong³, Jun Hwi Cho⁴, Moo-Ho Won⁵, Choong-Hyun Lee⁶

Affiliations

¹ Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, South Korea.
² Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
³ Department of Surgery, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
⁴ Department of Emergency Medicine and Institute of Medical Sciences, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
⁵ Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: mhwon@kangwon.ac.kr.
⁶ Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, South Korea. Electronic address: anaphy@dankook.ac.kr.

PMID: 26453128
DOI: 10.1016/j.jns.2015.10.001

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.

Keywords: Astrocytes; Excitotoxic neuronal damage; Microglia; Pro-inflammatory cytokines; Seizure; Serotonin/norepinephrine reuptake inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / drug effects*
CA3 Region, Hippocampal / drug effects*
Cell Death / drug effects
Disease Models, Animal
Duloxetine Hydrochloride / administration & dosage
Duloxetine Hydrochloride / pharmacology*
Excitatory Amino Acid Agonists / administration & dosage
Excitatory Amino Acid Agonists / toxicity*
Interleukin-1beta / drug effects*
Kainic Acid / administration & dosage
Kainic Acid / toxicity*
Male
Mice
Mice, Inbred ICR
Microglia / drug effects*
Neuroprotection / drug effects*
Serotonin and Noradrenaline Reuptake Inhibitors / administration & dosage
Serotonin and Noradrenaline Reuptake Inhibitors / pharmacology*
Tumor Necrosis Factor-alpha / drug effects*

Substances

Excitatory Amino Acid Agonists
Interleukin-1beta
Serotonin and Noradrenaline Reuptake Inhibitors
Tumor Necrosis Factor-alpha
Duloxetine Hydrochloride
Kainic Acid