Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

摘要
背景：癫痫常伴发抑郁、双相障碍及焦虑等神经精神共病。针对癫痫的药物或可用于治疗其神经精神共病。
目的：探讨5-羟色胺能调节对戊四氮（pentylenetetrazole, PTZ）诱导的大鼠癫痫模型中促炎细胞因子水平与癫痫发作的影响。
方法：雄性Wistar大鼠在予以戊四氮处理前30分钟，分别腹腔注射5-羟色胺、选择性5-羟色胺再摄取抑制剂氟西汀、5-HT1B/D受体激动剂舒马普坦或生理盐水。采用拉辛量表（Racine's scale）评估行为性癫痫发作。通过酶联免疫吸附测定（ELISA）检测血清与脑组织中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）及肿瘤坏死因子-α（TNF-α）的浓度。
结果：5-羟色胺与氟西汀（而非舒马普坦）可通过延长肌阵挛发作与全面性强直-阵挛发作的潜伏期，缓解戊四氮诱导的癫痫发作，且氟西汀的抗癫痫作用优于5-羟色胺。同理，5-羟色胺与氟西汀（而非舒马普坦）可降低戊四氮诱导的血清与脑组织中IL-1β及IL-6水平升高。所有受试药物（包括戊四氮）均未对TNF-α浓度产生显著影响。
结论：本研究结果提示，内源性与外源性5-羟色胺可通过抑制神经炎症发挥抗惊厥作用。5-HT1B/D受体似乎并不介导5-羟色胺的抗惊厥与抗神经炎症效应。