Raboisson P, Flood K, Lehmann A, Berge O G
Laboratoire de Physiologie Oro-Faciale, Faculté de Chirurgie Dentaire, Clermont-Ferrand, France.
J Neurosci Res. 1997 Aug 1;49(3):364-71.
N-methyl-D-aspartate (NMDA) receptor antagonists induce transient vacuole formation in neurons of the retrosplenial cortex and, after higher doses, necrosis in the same region. To our knowledge, all studies demonstrating these effects have been carried out in rats or mice. The present study investigated whether vacuolization occurs in the guinea pig, rats being used as controls. Female Dunkin-Hartley guinea pigs (age 15-18 weeks) were given a single subcutaneous injection of saline or the non-competitive NMDA antagonist dizocilpine maleate [(+)-MK-801; 1, 4, or 12 mg/kg]. Female Sprague-Dawley rats (age 16 weeks) received saline or MK-801 (1 mg/kg). Whatever the dose of MK-801, guinea pigs showed only occasional vacuolated neurons in the retrosplenial cortex. However, affected neurons (mainly large pyramidal cells of layer V) were found in the frontoparietal neocortex. The reaction was limited after 1 mg/kg, and seemed to reach a maximum at 4 mg/kg. Rats injected with 1 mg/kg MK-801 showed an intense vacuole reaction in neurons from layers III-IV of the retrosplenial cortex, but no affected neurons were noted in neocortical areas. We conclude that there are significant species differences in susceptibility to, and location of, vacuolization induced by NMDA receptor antagonists.
N-甲基-D-天冬氨酸（NMDA）受体拮抗剂可诱导脾后皮质神经元出现短暂的空泡形成，高剂量时则会导致该区域发生坏死。据我们所知，所有证明这些效应的研究均在大鼠或小鼠身上进行。本研究调查了豚鼠是否会出现空泡化，以大鼠作为对照。给15 - 18周龄的雌性Dunkin-Hartley豚鼠皮下单次注射生理盐水或非竞争性NMDA拮抗剂马来酸氯胺酮[（+）-MK-801；1、4或12毫克/千克]。16周龄的雌性Sprague-Dawley大鼠接受生理盐水或MK-801（1毫克/千克）。无论MK-801的剂量如何，豚鼠在脾后皮质中仅偶尔出现空泡化神经元。然而，在额顶叶新皮质中发现了受影响的神经元（主要是V层的大型锥体细胞）。1毫克/千克剂量时反应有限，4毫克/千克时似乎达到最大值。注射1毫克/千克MK-801的大鼠在脾后皮质III - IV层的神经元中出现强烈的空泡反应，但在新皮质区域未发现受影响的神经元。我们得出结论，NMDA受体拮抗剂诱导的空泡化在易感性和发生部位上存在显著的物种差异。
