Oosterink B J, Korte S M, Nyakas C, Korf J, Luiten P G
Department of Animal Physiology, Graduate School of Behavioral and Cognitive Neuroscience, University of Groningen, Haren, The Netherlands.
Eur J Pharmacol. 1998 Oct 2;358(2):147-52. doi: 10.1016/s0014-2999(98)00614-1.
The present study reports the neuroprotective efficacy of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ipsapirone against in vivo excitotoxic neuronal injury. Excitotoxic cell death was induced by injections of N-methyl-D-aspartate (NMDA) in the rat magnocellular nucleus basalis. The neurodegenerative effects were quantified by image analysis of the axonal density of the nucleus basalis projection to the somatosensory cortex visualized with acetylcholinesterase histochemistry. Pretreatment with 8-OH-DPAT--but not ipsapirone--1 h prior to NMDA infusion showed significant preservation of cortical cholinergic innervation in all doses tested. Furthermore, 8-OH-DPAT exhibited sustained efficacy under homeothermic conditions in which the body temperature was maintained at 36.8 +/- 0.1 degrees C. These data indicate that selective 5-HT1A receptor activation by 8-OH-DPAT protects against NMDA-induced excitotoxic neuronal damage, probably as a result of 5-HT1A receptor-mediated neuronal hyperpolarization.
本研究报告了5-羟色胺1A（5-HT1A）受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）和伊沙匹隆对体内兴奋性毒性神经元损伤的神经保护作用。通过向大鼠基底大细胞核注射N-甲基-D-天冬氨酸（NMDA）诱导兴奋性毒性细胞死亡。通过乙酰胆碱酯酶组织化学观察基底核投射到体感皮层的轴突密度，用图像分析法定量神经退行性变效应。在注入NMDA前1小时用8-OH-DPAT（而非伊沙匹隆）预处理，在所测试的所有剂量下均显示出对皮质胆碱能神经支配的显著保护作用。此外，8-OH-DPAT在体温维持于36.8±0.1℃的恒温条件下表现出持续的功效。这些数据表明，8-OH-DPAT选择性激活5-HT1A受体可保护神经元免受NMDA诱导的兴奋性毒性损伤，这可能是5-HT1A受体介导的神经元超极化的结果。
