Bupropion attenuates kainic acid-induced seizures and neuronal cell death in rat hippocampus

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 30min before the KA (15mg/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. •Bupropion attenuates kainic acid-induced seizures.•Bupropion reduces kainic acid-induced neuronal cell death.•Bupropion reduces kainic acid-induced microglia activation.•Bupropion reduces kainic acid-induced c-Fos expression and ERK1/2 phosphorylation.•Bupropion has anticonvulsant, anti-inflammatory, and neuroprotective effect.