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

在本研究中，实现了新的检查，旨在通过使用正电子发射断层扫描（PET）分析视觉中的兴奋剂诱导精神病的机制，并在今年取得了以下成果。(1)PET实验，使用正电子标记的甲基苯丙胺（MAP）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.编制了简单实用的PET图像融合分析程序。在该程序上启用了动力学分析。(2)检测用MAP逆转耐药模型动物1只。为研究MAP在致敏大鼠体内的分布，建立了MAP的气相色谱/质谱（GC/MS）微量测定方法。提示MAP增敏过程中存在脑、心特异性MAP分布改变.原位杂交检测EphA 5受体mRNA的变化。这种兴奋剂显示了通过EphA 5受体的变化引起神经系统可塑性变化的可能性。(3)脑组织胺系统检查1。受体基因敲除小鼠研究：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性。特别是，主张使用新的H3受体进行药物开发的新应用的可能性。

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.