Neural mechanisms of prefrontal dysfunction in animal models of schizophrenia

精神分裂症动物模型前额叶功能障碍的神经机制

• 批准号: 11670958
• 负责人: JODO Eiichi
• 金额: $ 0.77万
• 依托单位: Fukushima Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670958/
• 关键词: prefrontalcortex; hippocampus; subiculum; phencyclidine; MK801; NMDA receptor antagonist; reverse dialysis; animal model; methamphetamine; 電気生理学; フェンサイクリジン; PCP; 微小電気泳動; ユニット活動; ユニット記録; NMDA

Phencyclidine (PCP) is a well-known psychotomimetic drug, which induces schizophrenia-like symptoms in healthy individuals. PCP-administered animals are now considered as the most reliable pharmachological model of schizophrenia. This study aimed to investigate the neural mechanisms of prefrontal dysfunctions in rats with acute administration of PCP. Following four experiments were conducted. In the first experiment the single unit activity of medial prefrontal cortex (mPFC) neurons was recorded in freely moving rats before and after intraperitoneal injection of either PCP or saline. In the second experiment PCP was iontophoretically applied on mPFC neurons to examine the direct effects of PCP on firing activity of a single mPFC neuron in anesthetized rats. In the third experiment the single unit activity of mPFC neurons was recorded for systemic injection of a psychomotor stimulant, methamphetamine (MAP), to compare with the effects of PCP on firing activity of mPFC neurons. In the last experiment PCP or MK801 was locally perfused with a reverse microdyalysis method in the ventral hippocampus to examine the possible origin of excitatory inputs to the mPFC in freely moving rats. The results of these experiments were as follows. (1) Systemically-applied PCP produces long-lasting activation (> 70 min) of mPFC neurons (2) Microiontophoretically-applied PCP produces little change in firing activity of mPFC neurons (3) Systemically-applied MAP does not alter the firing rate in almost all mPFC neurons recorded, although locomotor activity are markedly increased (4) Relatively short-lasting activation of mPFC neurons is induced by local perfusion of PCP or MK801 in the ventral subiculum, but not in the ventral CA1 area. These results suggest that systemic PCP may induce tonic activation of mPFC neurons through excitatory inputs from the ventral subiculum.

苯环利定(PCP)是一种广为人知的拟精神分裂症药物，可在健康人中诱导精神分裂症样症状。PCP给药的动物现在被认为是精神分裂症最可靠的药理学模型。本研究旨在探讨PCP急性给药大鼠前额叶功能障碍的神经机制。随后进行了四个实验。在第一个实验中，记录了自由活动大鼠在腹腔注射PCP或生理盐水前后内侧前额叶皮质(MPFC)神经元的单位活动。实验二将PCP直接作用于麻醉大鼠mPFC神经元，观察PCP对单个mPFC神经元放电活动的直接影响。在第三个实验中，记录了全身注射精神运动兴奋剂甲基苯丙胺(MAP)时mPFC神经元的单位放电活动，以比较PCP对mPFC神经元放电活动的影响。在上一次实验中，用反向微动力学方法在腹侧海马区局部灌流PCP或MK801，以研究自由活动大鼠mPFC兴奋性输入的可能来源。这些实验的结果如下。(1)全身应用PCP可使mPFC神经元产生长时间的兴奋(约70分钟)；(2)微离子导入PCP对mPFC神经元的放电活动无明显影响；(3)全身应用MAP不改变几乎所有mPFC神经元的放电频率，尽管运动活动明显增加；(4)局部灌流PCP或MK801在腹侧下丘脑区可引起mPFC神经元较短时间的激活，但对腹侧CA1区无影响。这些结果提示，全身性PCP可能通过腹侧下丘脑的兴奋性传入引起mPFC神经元的紧张性激活。

项目成果

Eiichi Jodo: "Selective responsiveness of medial prefrontal cortex neurons to the meaningful stimulus with a low probability of occurrence in rats"Brain Research. 856. 68-74 (2000)

Eiichi Jodo：“内侧前额叶皮层神经元对大鼠中发生概率较低的有意义的刺激的选择性反应”大脑研究。

Y. Suzuki et al.: "Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats"Neuroscience. (in press).

Y. Suzuki 等人：“急性施用苯环己哌啶可诱导自由活动大鼠内侧前额皮质神经元的强直激活”《神经科学》。

Y.Suzuki et al.: "Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats"Neuroscience. (in press). (2002)

Y.Suzuki 等人：“急性施用苯环己哌啶可诱导自由活动大鼠内侧前额皮质神经元的强直激活”神经科学。

E. Jodo et al.: "Selective responsiveness of medial prefrontal cortex neurons to the meaningful stimulus with a low probability of occurrence in rats"Brain Research. 856. 68-74 (2000)

E. Jodo 等人：“内侧前额叶皮层神经元对有意义的刺激的选择性反应，在大鼠中发生的可能性较低”大脑研究。