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

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 10 mg/kg DXT reduced KA-induced neuronal death in the hippocampal CA3 region at 72 h after KA administration, and treatment with 20 and 40 mg/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.