RESEARCH ON NEUROTOXICITY OF NMDA ANTAGONIST AND THE EFFECTS OF ANESTHETICS ON THE NEUROTOXICITY

氯胺酮是一种非竞争性NMDA拮抗剂，具有拟精神活动(不良心理反应)。最近的研究表明，NMDA拮抗剂引起扣带回皮质的形态损伤，这被认为是其拟精神活动的负责脑区域。在本研究中，我们证明了氯胺酮可诱导大鼠扣带回c-fos蛋白的表达，c-fos被认为是一个很好的代谢标记物。我们还证明了临床剂量的安定、氟烷和异丙酚以剂量依赖的方式抑制这种诱导。这些结果为这些药物阻止氯胺酮诱导的拟精神活动提供了神经元基础。

Ketamine, a noncompetitive NMDA antagonist, has psychotomimetic activity (undesirable psychological reactions). Recent studies have shown that NMDA antagonists cause morphological damages in the cingulate cortex, which is suggested to be the responsible brain region for their psychotomimetic activity. In the present research, we have demonstrated that ketamine induced marked c-fos protein (c-Fos) expression, which is suggested to be a good metabolic marker, in the rat cingulate cortex. We also demonstrated that diazepam, halothane, and propofol at clinical doses inhibited the induction in a dose-dependent manner. These results provide the neuronal basis that these drugs prevent ketamine-induced psychotomimetic activity.