Baran H, Sperk G, Hörtnagl H, Sapetschnig G, Hornykiewicz O
Eur J Pharmacol. 1985 Jul 17;113(2):263-9. doi: 10.1016/0014-2999(85)90744-7.
We have tested several compounds interfering with the brain monoamine (noradrenaline, dopamine, serotonin) and acetylcholine systems for their effects on limbic seizures produced by systemically (s.c.) injected kainic acid as well as on neurochemical changes in amygdala/pyriform cortex resulting from the kainic acid treatment. The characteristic neurochemical changes induced by s.c. kainic acid were a decrease in noradrenaline and an increase in 5-hydroxyindoleacetic acid in the acute (3 h after kainic acid injection) suggesting strongly increased neurotransmitter turnover in noradrenergic and serotonergic neurons. This was followed by a reduction of glutamic acid decarboxylase and choline acetyltransferase activities during the chronic phase (3 days) of the kainic acid action, indicating destruction of GABAergic and cholinergic neurons. The compounds tested in this model of limbic epilepsy included 1-propranolol, prazosin, clonidine, yohimbine, metergoline, atropine and haloperidol. Among these compounds the alpha 2-adrenergic agonist clonidine (0.1 mg/kg, i.p.) exhibited a powerful protective action on kainic acid-induced limbic seizures as well as on the neurochemical changes in the amygdala and pyriform cortex. In addition, the adrenoceptor antagonists prazosin (alpha 1) and propranolol (beta) as well as the dopamine receptor antagonist haloperidol had significant but less potent - protective actions upon kainic acid-induced seizures and subsequent neurochemical changes. On the other hand, yohimbine (alpha 2-antagonist) and metergoline (serotonin-antagonist) potentiated the limbic seizure syndrome and no effect was found with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)
我们已经测试了几种干扰大脑单胺（去甲肾上腺素、多巴胺、血清素）和乙酰胆碱系统的化合物，观察它们对全身（皮下）注射红藻氨酸所引发的边缘叶癫痫发作的影响，以及对红藻氨酸处理后杏仁核/梨状皮质神经化学变化的影响。皮下注射红藻氨酸所引发的典型神经化学变化是，在急性期（注射红藻氨酸后3小时）去甲肾上腺素减少，5-羟吲哚乙酸增加，这强烈表明去甲肾上腺素能和血清素能神经元的神经递质周转率大幅提高。随后，在红藻氨酸作用的慢性期（3天），谷氨酸脱羧酶和胆碱乙酰转移酶活性降低，表明γ-氨基丁酸能和胆碱能神经元遭到破坏。在这个边缘叶癫痫模型中测试的化合物包括普萘洛尔、哌唑嗪、可乐定、育亨宾、麦角新碱、阿托品和氟哌啶醇。在这些化合物中，α2-肾上腺素能激动剂可乐定（0.1毫克/千克，腹腔注射）对红藻氨酸诱导的边缘叶癫痫发作以及杏仁核和梨状皮质的神经化学变化表现出强大的保护作用。此外，肾上腺素能受体拮抗剂哌唑嗪（α1）和普萘洛尔（β）以及多巴胺受体拮抗剂氟哌啶醇对红藻氨酸诱导的癫痫发作及随后的神经化学变化具有显著但较弱的保护作用。另一方面，育亨宾（α2拮抗剂）和麦角新碱（血清素拮抗剂）增强了边缘叶癫痫综合征，而阿托品则没有效果。（摘要截取自250字）
