2002 Fiscal Year Final Research Report Summary
Investigation of mechanism of stimulant-induced psychosis -Imaging study by PET -
| Project/Area Number |
12557227
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
HISHINUMA Takanori Tohoku University Hospital, Associate Professor, 医学部附属病院, 助教授 (20199003)
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| Co-Investigator(Kenkyū-buntansha) |
YANAI Kazuhiko Tohoku University, graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50192787)
ITO Masatoshi Tohoku University, Cyclotron and Radioisotope Center, Professor, サイクロトロンラジオアイソトープセンター, 教授 (00125501)
IDO Tatsuo Tohoku University, Cyclotron and Radioisotope Center, Professor, サイクロトロンラジオアイソトープセンター, 教授 (80134063)
MIZUGAKI Michinao Tohoku Pharmaceutical University, Professor, 薬学部, 教授 (60004595)
NUMACHI Yotaro Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (00261636)
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| Project Period (FY) |
2000 – 2002
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| Keywords | methamphetamine / sensitization / PET / Histamine / EphA5 / imaging / anesthesia / GC-MS |
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| Research Abstract |
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 animal
1. 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 brain
1. 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.
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