Morimoto K, Katayama K, Inoue K, Sato K
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Pharmacol Biochem Behav. 1991 Dec;40(4):893-9. doi: 10.1016/0091-3057(91)90103-9.
In the present study, comparative studies of the effects of competitive and noncompetitive antagonists of NMDA receptors (CPP, CGS19755 and MK-801) on two models of neuronal plasticity, kindling and long-term potentiation (LTP), were performed in rats. Systemic administration of CPP (5, 10 mg/kg), CGS19755 (5, 10 mg/kg) or MK-801 (1, 2 mg/kg) strongly retarded kindling development from the amygdala (AM), in which the early stage of kindled seizures and the growth of afterdischarges (ADs) recorded from the AM were significantly suppressed. After establishment of kindling, however, these compounds only reduced the previously AM-kindled seizure stage without shortening the AD duration. These NMDA receptor antagonists with the same dose sufficient for suppressing AM kindling almost completely blocked LTP of the synaptic component in the hippocampal dentate gyrus following high-frequency trains of the perforant path in urethane-anesthetized rats. These results further support the hypothesis that neuronal plasticity is induced by activation of the NMDA receptor complex and one of the basic neuronal mechanisms underlying kindling may be a long-lasting increase in synaptic transmission.
在本研究中，我们在大鼠身上进行了对比研究，观察NMDA受体的竞争性拮抗剂和非竞争性拮抗剂（CPP、CGS19755和MK-801）对两种神经元可塑性模型，即点燃和长时程增强（LTP）的影响。全身性给予CPP（5、10mg/kg）、CGS19755（5、10mg/kg）或MK-801（1、2mg/kg）可显著延缓杏仁核（AM）点燃的发展，其中AM记录到的点燃性癫痫早期阶段和后放电（ADs）的增长均受到显著抑制。然而，在点燃建立后，这些化合物仅降低了先前由AM点燃的癫痫发作阶段，而未缩短AD持续时间。在乌拉坦麻醉的大鼠中，给予足以几乎完全抑制AM点燃的相同剂量的这些NMDA受体拮抗剂，可几乎完全阻断高频串刺激穿通路径后海马齿状回突触成分的LTP。这些结果进一步支持了以下假说：神经元可塑性是由NMDA受体复合物的激活所诱导，点燃背后的基本神经元机制之一可能是突触传递的长期增加。
