Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University), New Delhi, India.
Hum Exp Toxicol. 2019 Mar;38(3):336-346. doi: 10.1177/0960327118814149. Epub 2018 Nov 25.
Serotonin (5-hydroxytrytamine (5-HT)) plays an important role in experimental seizures. Recently, we reported the depletion of 5-HT by parachlorophynylalanine (PCPA) in whole brain to enhance 6-Hz psychomotor seizures in mice. In the present work, we investigated the effect of 5-HT depletion in cortex and hippocampus, brain regions relevant for epilepsy, on behavioral and ultra-structural changes following 6-Hz psychomotor seizures in mice. In addition, we studied the effect of sodium valproate (SVP) on behavioral, biochemical, and ultra-structural effects induced by 6 Hz. Behavioral changes induced by 6 Hz stimulation were characterized as the increased duration of Straub's tail, stun position, twitching of vibrissae, forelimb clonus, and increased rearing and grooming. PCPA administration further enhanced while SVP reduced these behaviors in mice. The 6-Hz psychomotor seizure induced ultra-structural changes in both cortex and hippocampus in mice treated with PCPA. Furthermore, PCPA administrations followed by 6Hz-induced seizures were accompanied by reduced hippocampal and cortical 5-HT. SVP attenuated the PCPA-induced ultra-structural changes and alterations of 5-HT content in the mouse brain. The study suggests the involvement of 5-HT in the 6 Hz psychomotor seizures and in the mechanisms of action of SVP against such seizures in mice.
5-羟色胺（5-HT）在实验性癫痫发作中起着重要作用。最近，我们报道了全脑用对氯苯丙氨酸（PCPA）耗竭 5-HT 以增强小鼠的 6-Hz 运动性癫痫发作。在本工作中，我们研究了脑皮质和海马中 5-HT 耗竭（与癫痫相关的脑区）对 6-Hz 运动性癫痫发作后行为和超微结构变化的影响。此外，我们研究了丙戊酸钠（SVP）对 6 Hz 诱导的行为、生化和超微结构影响的作用。6 Hz 刺激引起的行为变化表现为 Straub 尾巴持续时间增加、昏迷姿势、触须抽搐、前肢阵挛和增加的后肢和梳理行为。PCPA 给药进一步增强了 SVP 在小鼠中的这些行为。6-Hz 运动性癫痫发作在给予 PCPA 的小鼠的皮质和海马中均引起超微结构变化。此外，在给予 PCPA 后进行 6Hz 诱导的癫痫发作伴随着海马和皮质 5-HT 的减少。SVP 减轻了 PCPA 诱导的超微结构变化和小鼠脑内 5-HT 含量的改变。该研究表明 5-HT 参与了 6-Hz 运动性癫痫发作，以及 SVP 对小鼠此类癫痫发作的作用机制。
