Gharib Alireza, Sayyahi Zeinab, Komaki Alireza, Barkley Victoria, Sarihi Abdolrahman, Mirnajafi-Zadeh Javad
Department of Physiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Physiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Physiol Behav. 2018 Nov 1;196:119-125. doi: 10.1016/j.physbeh.2018.08.025. Epub 2018 Sep 1.
Low frequency stimulation (LFS) has been proposed as a method in the treatment of epilepsy, but its anticonvulsant mechanism is still unknown. In the current study, the hippocampal CA1 region was microinjected with NAD-299 (a selective 5-HT antagonist), and its role in mediating the inhibitory action of LFS on amygdala kindling was investigated. Male Wistar rats were kindled by amygdala stimulation in a semi-rapid kindling manner (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, 50-150 μA) was applied at 5 min after termination of daily kindling stimulations. NAD (a selective 5-HT antagonist) was microinjected into the CA1 region of the hippocampus at the doses of 2.5 and 5 μg/1 μl. An open field test was also run to determine the motor activity of animals in different experimental groups. The application of LFS following daily kindling stimulations reduced the behavioral seizure stages, afterdischarge duration, and stage 5 seizure duration and increased the latency to stage 4 seizure compared to the kindled group. However, microinjection of NAD at the doses of 5 μg/1 μl, but not 2.5 μg/1 μl, blocked the inhibitory effect of LFS on behavioral and electrophysiological parameters in kindled animals. It could be presumed that 5-HT receptors in the CA1 area are involved in mediating the antiepileptic effects of LFS.
低频刺激（LFS）已被提议作为一种治疗癫痫的方法，但其抗惊厥机制仍不清楚。在本研究中，向海马CA1区微量注射NAD - 299（一种选择性5 - 羟色胺拮抗剂），并研究其在介导LFS对杏仁核点燃的抑制作用中的作用。雄性Wistar大鼠以半快速点燃方式（每天12次刺激）通过杏仁核刺激进行点燃。在每日点燃刺激结束后5分钟施加LFS（1赫兹，0.1毫秒脉冲持续时间，200个脉冲，50 - 150微安）。将NAD（一种选择性5 - 羟色胺拮抗剂）以2.5和5微克/1微升的剂量微量注射到海马CA1区。还进行了旷场试验以确定不同实验组动物的运动活动。与点燃组相比，每日点燃刺激后施加LFS降低了行为性癫痫发作阶段、放电后持续时间和5期癫痫发作持续时间，并增加了4期癫痫发作的潜伏期。然而，以5微克/1微升而非2.5微克/1微升的剂量微量注射NAD可阻断LFS对点燃动物行为和电生理参数的抑制作用。可以推测，CA1区的5 - 羟色胺受体参与介导LFS的抗癫痫作用。
