Kapur J, Michelson H B, Buterbaugh G G, Lothman E W
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
Epilepsy Res. 1989 Sep-Oct;4(2):90-9. doi: 10.1016/0920-1211(89)90013-2.
Rats were kindled with either of 2 protocols: (1) a rapidly recurring hippocampal seizure (RRHS) paradigm in which 10 sec stimulus trains were delivered every 5 min through hippocampal electrodes; and (2) a traditional approach in which 1 sec stimulus trains were given to the amygdala once daily. Three groups of kindled rats were prepared: (1) one of amygdala-kindled rats that had experienced 9-15 seizures; (2) one of RRHS-kindled rats that had experienced 96 seizures; and (3) one of RRHS-overkindled rats that had experienced 144-336 seizures. After a 1 month seizure-free period, the animals were anesthetized with urethane and measurements were made on the potency of paired pulse inhibition in the CA1 region of the hippocampus. All groups of kindled animals were found to have significantly less paired pulse inhibition than control rats. This decrement was confined to interpulse intervals less than or equal to 70 msec. The amount of inhibition lost correlated with the number of seizure that had occurred. The GABAergic agonist muscimol restored paired pulse inhibition in kindled animals for interpulse intervals less than or equal to 70 msec towards normal values. These results indicate that not only RRHS, but also other modes of kindling, reduced GABAergic inhibition in the CA1 region of the hippocampus and that this diminution was long-lasting, if not permanent.
（1）快速反复海马癫痫发作（RRHS）范式，即每隔5分钟通过海马电极给予10秒的刺激串；（2）传统方法，即每天向杏仁核给予1秒的刺激串。制备了三组点燃大鼠：（1）一组经历了9 - 15次癫痫发作的杏仁核点燃大鼠；（2）一组经历了96次癫痫发作的RRHS点燃大鼠；（3）一组经历了144 - 336次癫痫发作的RRHS过度点燃大鼠。在1个月无癫痫发作期后，用乌拉坦麻醉动物，并测量海马CA1区配对脉冲抑制的效能。发现所有点燃动物组的配对脉冲抑制均明显低于对照大鼠。这种减少仅限于脉冲间隔小于或等于70毫秒的情况。丧失的抑制量与发生的癫痫发作次数相关。GABA能激动剂蝇蕈醇使点燃动物在脉冲间隔小于或等于70毫秒时的配对脉冲抑制恢复到正常值。这些结果表明，不仅RRHS，而且其他点燃模式，都会降低海马CA1区的GABA能抑制，并且这种减少即使不是永久性的，也是长期存在的。
