AMPA receptor activation reduces epileptiform activity in the rat neocortex

被引:11
作者
Addae, Jonas I. [1 ]
Ali, Nakisha
Youssef, Farid F.
Stone, Trevor W.
机构
[1] Univ West Indies, Fac Med Sci, Dept Preclin Sci, St Augustine, Trinidad Tobago
[2] Univ Glasgow, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
关键词
AMPA; NMDA; GABA; clomethiazole; epilepsy; neocortex; EXCITATORY AMINO-ACIDS; EVOKED-POTENTIALS; DESENSITIZATION; HIPPOCAMPAL; VULNERABILITY; DEPRESSION; MODULATORS; NEURONS; CA1;
D O I
10.1016/j.brainres.2007.05.002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have previously reported that topical application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to the rat neocortex prevents the effects of a subsequent application of N-methyl-D-aspartic acid (NMDA). Activation of NMDA receptors is involved in the pathogenesis of epileptic activity. Therefore, we examined if topically applied AMPA could affect changes in the somatosensory evoked potentials (SEPs) and electrocorticogram (ECoG) epileptic spikes caused by bicuculline. AMPA (50 mu M) prevented the epileptiform activity to a level that was comparable to that caused by diazepam (3 mg/kg i.p.) or clomethiazole (100 mg/kg i.p.). Also, the epileptiform activity was suppressed by the AMPAR antagonist, CNQX, or the blocker of AMPAR desensitization, cyclothiazide. in the hippocampal slice, bicuculline-incluced changes in the population spike potentials recorded from the CA1 cells were not affected by AMPA. We conclude that in the complex neuronal network of the rat neocortex, epileptiform activity can be suppressed in a variety of strategies that target the AMPA receptors: (1) blocking AMPA receptors, (2) promoting an apparent desensitization of AMPA receptors (possibly on the pyramidal neurons) or (3) reducing an apparent desensitization of AMPA receptors (possibly on the inhibitory GABAergic interneurons). (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:151 / 157
页数:7
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