Investigation of mechanism of stimulant-induced psychosis -Imaging study by PET -

本研究利用正电子发射断层扫描(PET)技术对兴奋剂所致视觉性精神病的发病机制进行了新的研究，取得了以下成果：(1)正电子标记甲基苯丙胺(MAP)的正电子发射断层扫描实验1.氟哌啶醇预处理可阻止致敏动物脑内[UC]MAP摄取的显著增加。在PET中开发了简单实用的图像融合和分析程序。在该程序上实现了动力学分析。(2)检测采用MAP反向抗性模型Animal1。为了阐明MAP在MAP致敏大鼠体内的分布，我们建立了MAP微量气相色谱/质谱仪(GC/MS)测定方法。可见，MAP敏化过程中，大脑和心脏发生了特异性的MAP分布改变。用原位杂交法检测EPHA5受体基因表达的变化。刺激剂可能通过EPHA5受体的改变引起神经系统的可塑性改变。(3)大脑中的组胺系统检查1。受体敲除小鼠研究：利用组胺受体基因敲除小鼠阐明组胺在中枢神经系统中的作用。阐明了组胺H3受体和组胺转运体的特点。特别是提出了新的H3受体在药物开发中应用的可能性。

In this research, novel examinations were achieved aiming to analyze the mechanism of the stimulant induced psychosis in the sight by using positron emission tomography (PET) and the following results were achieved this year.(1) PET experiment that used positron labeled methamphetamine (MAP)1. A significant increase of [UC]MAP uptake into the sensitized animal brain was prevented by haloperidol pretreatments.2. Simple, useful image fusion and analysis program were developed in PET. The kinetic analysis was enabled on this program.(2) Examination used the MAP reverse resistant model animal1. To elucidate the MAP distribution in the MAP sensitized rat we established the MAP-microdetermination method using gas chromatography/mass spectrometry (GC/MS). It was clear that the brain and heart specific alteration of the MAP distribution occurred in the MAP sensitization.2. Changing mRNA of the EphA5 receptor was examined by in situ hybridization method. The stimulant showed the possibility of causing a plastic change in the nerve system through the change in the EphA5 receptor.(3) Histamine system examination in the brain1. The receptor knockout mouse research : The role in the central nervous system of histamine was clarified using the histamine receptor gene knockout mouse.2. The feature of histamine H3 receptor and the histamine transporter was clarified. Especially, the possibility of a new application of the drug development with a new H3 receptor was advocated.