Saucier D, Cain D P
Department of Psychology, University of Western Ontario, London, Canada.
Epilepsy Res. 1996 May;24(1):9-18. doi: 10.1016/0920-1211(95)00106-9.
The role of NMDA receptor activity in kindling was examined in rats pretreated with the competitive NMDA receptor antagonists aminophosphonovaleric acid (APV) or NPC17742 (2R,4R,2S-(2-amino-4,5(cyclohexyl)-7-phosphonoheptanoic acid). After pretreatment, the rats received an infusion of carbachol, a muscarinic agonist, into the amygdala or hippocampus. Kindling sessions with carbachol occurred once every 48 h until a stage 5 convulsion was displayed. Electrical kindling of the amygdala after pretreatment with NPC17742 was also examined. Both APV and NPC17742 retarded the rate of carbachol kindling in its early stages, but all rats displayed kindled stage 5 convulsions under APV or NPC17742 in fewer than 10 sessions. Convulsion development was accompanied by growth in the duration and strength of the accompanying epileptiform activity. All rats exhibited a stage 5 convulsion on the first or second session after cross-over to vehicle pretreatment, confirming the development of kindled convulsions under pretreatment with NMDA antagonists. NPC17742 retarded electrical kindling, but after cross-over to vehicle there was savings in the rate of kindling to stage 5 convulsions. These findings indicate that carbachol kindling of the amygdala or hippocampus readily occurs under NMDA antagonism. They are consistent with the view that NMDA receptor activity may contribute to, but is not required for, the kindling of seizures.
在预先用竞争性NMDA受体拮抗剂氨基磷酸戊酸（APV）或NPC17742（2R,4R,2S-(2-氨基-4,5(环己基)-7-磷酸庚酸)）处理的大鼠中，研究了NMDA受体活性在点燃中的作用。预处理后，给大鼠杏仁核或海马体注射毒蕈碱激动剂卡巴胆碱。每隔48小时进行一次卡巴胆碱点燃实验，直到出现5级惊厥。还研究了用NPC17742预处理后杏仁核的电点燃情况。APV和NPC17742在早期都延缓了卡巴胆碱点燃的速度，但在APV或NPC17742作用下，所有大鼠在少于10次实验中都出现了5级点燃惊厥。惊厥发展伴随着伴随的癫痫样活动的持续时间和强度增加。所有大鼠在改用溶剂预处理后的第一或第二次实验中都出现了5级惊厥，证实了在NMDA拮抗剂预处理下点燃惊厥的发展。NPC17742延缓了电点燃，但改用溶剂后，点燃至5级惊厥的速度有所加快。这些发现表明，在NMDA拮抗作用下，杏仁核或海马体的卡巴胆碱点燃很容易发生。它们与以下观点一致，即NMDA受体活性可能有助于癫痫发作的点燃，但不是必需的。
