Applegate C D, Burchfiel J L
Department of Neurology, University of Rochester, NY 14642.
Epilepsy Res. 1990 May-Jun;6(1):23-32. doi: 10.1016/0920-1211(90)90005-g.
Kindling antagonism' is a modification of the standard kindling paradigm in which two limbic system structures are stimulated on alternate trials. The consistent outcome of this procedure is that one site ('dominant site') develops typical generalized seizures, while kindled seizure development from the other site ('suppressed site') is arrested at an intermediate stage. Our recent research suggests that kindling antagonism is dependent on hindbrain norepinephrine (NE) systems. The present study explores this relationship further. Neonatal rats were treated with intracerebral injections of 6-hydroxydopamine (6-OHDA). At adulthood, these animals received either (1) a low dose of 6-OHDA (75 micrograms), (2) a high dose of 6-OHDA (200 micrograms), or (3) vehicle. Regional NE concentrations were determined by high pressure liquid chromatography. Neonatal 6-OHDA followed by vehicle resulted in decreases in forebrain and increases in hindbrain NE concentrations. Low dose 6-OHDA at adulthood depleted cerebellar, but not pontine-medullary NE. High dose 6-OHDA resulted in depletions of both cerebellar and pontine-medullary NE. Only high dose 6-OHDA significantly interfered with the development of antagonism. Neonatal 6-OHDA facilitated the rate of dominant site kindling independently of subsequent adult treatment regimens. Results suggest that the influence of NE on kindling antagonism is mediated through a brain-stem substrate and that the influence of NE on kindling rate is mediated through a forebrain substrate.
“点燃拮抗作用”是对标准点燃范式的一种改良，即在交替试验中对两个边缘系统结构进行刺激。该程序的一致结果是，一个位点（“优势位点”）会出现典型的全身性癫痫发作，而另一个位点（“受抑制位点”）的点燃性癫痫发作发展则在中间阶段停止。我们最近的研究表明，点燃拮抗作用依赖于后脑去甲肾上腺素（NE）系统。本研究进一步探讨了这种关系。对新生大鼠进行脑内注射6-羟基多巴胺（6-OHDA）处理。成年后，这些动物分别接受（1）低剂量的6-OHDA（75微克）、（2）高剂量的6-OHDA（200微克）或（3）溶剂。通过高压液相色谱法测定区域NE浓度。新生期注射6-OHDA后再注射溶剂会导致前脑NE浓度降低，后脑NE浓度升高。成年期低剂量6-OHDA会使小脑NE耗竭，但不会使脑桥-延髓NE耗竭。高剂量6-OHDA会导致小脑和脑桥-延髓NE均耗竭。只有高剂量6-OHDA显著干扰了拮抗作用的发展。新生期6-OHDA促进了优势位点的点燃速率，且与后续成年期治疗方案无关。结果表明，NE对点燃拮抗作用的影响是通过脑干基质介导的，而NE对点燃速率的影响是通过前脑基质介导的。
