Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. A proposed risk marker for SUDEP is the duration of post-ictal generalized EEG suppression (PGES). The mechanisms underlying PGES are unknown. Serotonin (5-HT) has been implicated in SUDEP pathophysiology. Seizures suppress activity of 5-HT neurons in the dorsal raphe nucleus (DRN). We hypothesized that suppression of DRN 5-HT neuron activity contributes to PGES and increasing 5-HT neurotransmission or stimulating the DRN before a seizure would decrease PGES duration. Adult C57BL/6J and Pet1-Cre mice received EEG/EMG electrodes, a bipolar stimulating/recording electrode in the right basolateral amygdala, and either a microdialysis guide cannula or an injection of adeno-associated virus (AAV) allowing expression of channelrhodopsin2 plus an optic fiber into the DRN. Systemic application of the selective 5-HT reuptake inhibitor citalopram (20 mg/kg) decreased PGES duration from seizures induced during wake (n = 23) and non-rapid eye movement (NREM) sleep (n = 13) whereas fluoxetine (10 mg/kg) pretreatment decreased PGES duration following seizures induced from wake (n = 11), but not NREM sleep (n = 9). Focal chemical (n = 6) or optogenetic (n = 8) stimulation of the DRN reduced PGES duration following seizures in kindled mice induced during wake. During PGES, animals exhibited immobility and suppression of EEG activity that was reduced by citalopram pretreatment. These results suggest 5-HT and the DRN may regulate PGES.

癫痫猝死（SUDEP）是难治性癫痫患者死亡的主要原因。建议的 SUDEP 风险标志是发作后全身性脑电图抑制 (PGES) 的持续时间。PGES 的潜在机制尚不清楚。血清素 (5-HT) 与 SUDEP 的病理生理学有关。癫痫发作抑制中缝背核 (DRN) 中 5-HT 神经元的活动。我们假设 DRN 5-HT 神经元活动的抑制有助于 PGES 和增加 5-HT 神经传递或在癫痫发作前刺激 DRN 会减少 PGES 持续时间。成人 C57BL/6J 和Pet1-Cre小鼠接受 EEG/EMG 电极、右侧基底外侧杏仁核中的双极刺激/记录电极、微透析导管或腺相关病毒 (AAV) 注射，允许通道视紫红质 2 和光纤表达进入 DRN。全身应用选择性 5-HT 再摄取抑制剂西酞普兰 (20 mg/kg) 可减少觉醒期间 (n = 23) 和非快速眼动 (NREM) 睡眠 (n = 13) 期间诱发的癫痫发作的 PGES 持续时间，而氟西汀 (10 mg) /kg) 预处理减少了觉醒后癫痫发作后的 PGES 持续时间 (n = 11)，但不是 NREM 睡眠 (n = 9)。DRN 的局部化学 (n = 6) 或光遗传学 (n = 8) 刺激减少了在唤醒期间诱发的点燃小鼠癫痫发作后的 PGES 持续时间。在 PGES 期间，动物表现出不动和脑电图活动的抑制，西酞普兰预处理降低了这些活动。这些结果表明 5-HT 和 DRN 可能调节 PGES。