Mishra Awanish, Goel Rajesh Kumar
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Lucknow, India.
J Epilepsy Res. 2019 Dec 31;9(2):119-125. doi: 10.14581/jer.19012. eCollection 2019 Dec.
Recent studies have recognised the memory deficit as one of the most common psychiatric issues in the patients with epilepsy, which severely affects the quality of life. Our previous studies have demonstrated the possible involvement of serotonergic system in the pathogenesis of epilepsy and associated memory deficit. The possible involvement of 5-HT and 5-HT receptor has not been explored yet. Therefore, this study has been envisaged to explore the effect of 5-HT and 5-HT receptor modulation on epilepsy and memory deficit in pentylenetetrazole-kindled mice.
In the present experimental approach, we examined the efficacy of modulation of 5-HT and 5-HT receptor in pentylenetetrazole-induced kindling in male Swiss mice (n=75). Mice were kindled by sub-convulsive dose of pentylenetetrazole (35 mg/kg, intraperitoneal injection), at the interval of 48±2 hours). Successfully kindled animals were treated with 5-HT and 5-HT receptor modulators. The effect of different treatments on seizure severity score and memory impairment was analysed.
5-HT receptor agonist improved the memory functions while seizure severity was not improved, and the opposite effect was observed with 5-HT receptor antagonist. On the other hand, 5-HT receptor agonist significantly improved memory deficit as well as seizure severity in the kindled animals.
The outcome of the study indicates the possible involvement of 5-HT receptor in the pathogenesis of epilepsy and associated memory deficit, which can be further explored for its management.
近期研究已认识到记忆缺陷是癫痫患者最常见的精神问题之一，严重影响生活质量。我们之前的研究已证明血清素能系统可能参与癫痫发病机制及相关记忆缺陷。5-羟色胺（5-HT）和5-HT受体的可能参与情况尚未得到探索。因此，本研究旨在探讨5-HT和5-HT受体调节对戊四氮点燃小鼠癫痫及记忆缺陷的影响。
在本实验方法中，我们检测了5-HT和5-HT受体调节对雄性瑞士小鼠（n = 75）戊四氮诱导点燃的效果。小鼠通过亚惊厥剂量的戊四氮（35 mg/kg，腹腔注射）点燃，间隔时间为48±2小时。成功点燃的动物用5-HT和5-HT受体调节剂进行治疗。分析了不同治疗对癫痫发作严重程度评分和记忆损害的影响。
5-HT受体激动剂改善了记忆功能，但癫痫发作严重程度未改善，而5-HT受体拮抗剂则观察到相反的效果。另一方面，5-HT受体激动剂显著改善了点燃动物的记忆缺陷以及癫痫发作严重程度。
该研究结果表明5-HT受体可能参与癫痫发病机制及相关记忆缺陷，可进一步探索其在治疗方面的作用。
