Gulec Suyen Guldal, Isbil-Buyukcoskun Naciye, Kahveci Nevzat, Sengun Ece, Ozluk Kasim
Acibadem University School of Medicine, Department of Physiology, Istanbul, Turkey.
Uludag University School of Medicine, Department of Physiology, Bursa, Turkey.
Pharmacol Biochem Behav. 2016 Sep;148:128-35. doi: 10.1016/j.pbb.2016.07.003. Epub 2016 Jul 15.
In the present study, we aimed to investigate the effects of immediate and delayed treatment with intracerebroventricular (i.c.v.) gabapentin (GBP), carbamazepine (CBZ) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on learning and memory, anxiety, and locomotor activity in rats with lithium-pilocarpine-induced status epilepticus (SE). SE was induced by intraperitoneal injections of 3mEq/kg LiCl followed by 45mg/kg pilocarpine 24h later. In the first series of experiments, rats were divided into four groups three hours after the onset of SE and received GBP (100μg/10μl, two times a day; i.c.v.), CBZ (200μg/10μl; i.c.v.), CNQX (25nmol/10μl; i.c.v.) or saline (10μl; i.c.v.) for 7days. Six weeks after SE, cognitive and behavioral performances were evaluated by Morris water maze, elevated plus maze, and open field tests. In the second series, rats received no treatment for six weeks following SE. On the seventh week the same treatment with the previous rats was given and six weeks later the cognitive and behavioral tests were applied. SE significantly impaired spatial learning and memory in the Morris water maze. GBP treatment improved the acqusition and memory performance. CNQX worsened the acqusition but improved the memory performance, while CBZ worsened both parameters. In the elevated plus maze, epileptic rats which received saline showed significantly lower anxiety levels with respect to the naive rats. Only CBZ led to further anxiolysis, while the other drugs had no effect. Locomotor activity significantly increased due to SE, which was augmented by GBP and CNQX. The impact of immediate and delayed treatment with these drugs on cognition and behavior seems to be quite similar.
在本研究中,我们旨在探讨脑室内(i.c.v.)注射加巴喷丁(GBP)、卡马西平(CBZ)和6-氰基-7-硝基喹喔啉-2,3-二酮(CNQX)即刻和延迟治疗对锂-匹罗卡品诱导的癫痫持续状态(SE)大鼠学习记忆、焦虑及运动活动的影响。通过腹腔注射3mEq/kg氯化锂,24小时后再注射45mg/kg匹罗卡品诱导SE。在第一组实验中,SE发作3小时后将大鼠分为四组,分别接受GBP(100μg/10μl,每天两次;i.c.v.)、CBZ(200μg/10μl;i.c.v.)、CNQX(25nmol/10μl;i.c.v.)或生理盐水(10μl;i.c.v.)治疗7天。SE发作6周后,通过莫里斯水迷宫、高架十字迷宫和旷场试验评估认知和行为表现。在第二组实验中,SE发作后6周大鼠不接受治疗。第7周给予与前一组大鼠相同的治疗,6周后进行认知和行为测试。SE显著损害了莫里斯水迷宫中的空间学习和记忆能力。GBP治疗改善了学习和记忆表现。CNQX使学习能力恶化但改善了记忆表现,而CBZ使两个参数都恶化。在高架十字迷宫中,接受生理盐水治疗的癫痫大鼠相对于未处理大鼠焦虑水平显著降低。只有CBZ导致进一步的抗焦虑作用,而其他药物无此效果。SE导致运动活动显著增加,GBP和CNQX使其进一步增强。这些药物即刻和延迟治疗对认知和行为的影响似乎非常相似。