| Project/Area Number |
04670691
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | GUNMA UNIVERSITY |
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Principal Investigator |
HIGUCHI Teruhiko GUNMA UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (90105883)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIYOSHI Katsumi GUNMA UNIVERSITY, SCHOOL OF MEDICINE, INSTRUCTOR, 医学部, 助手 (60188802)
IDA Itsuro GUNMA UNIVERSITY, SCHOOL OF MEDICINE, INSTRUCTOR, 医学部, 助手 (50251103)
宮本 正典 群馬大学, 医学部, 助手 (10219818)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | ^<31>P-MRS / PME / Pi response / 5HT_2 receptor supersensitivity / chronic immobilized stress / affective disorders / メチラポン / 感情障害 / PDE / 5HT_2受容体 / ストレス / グルココルチコイド |
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| Research Abstract |
Although a lot of investigations of 5HT_2 receptor supersensitivity in affective disorders have been reported, almost findings except the direct measurement of 5HT_2 receptors in platelets of depressed patients. Recent progress in imaging modalities revolutinalizes our capacity to understand the functional changes of receptors and the 2nd messenger system in vivo. Especially, NMR spectroscopy can be developed as a tool to monitor 2nd messenger system in vivo.
In this project, firstly, we investigated whether the accumulation of inositol-1-phosphate can be detected by in vivo ^<31>P-MRS.5HT_2 agonist (DOI) was found to increase the level of PME and the difference of PME peak stimulated by DOI and not stimulated can be attributed to an increase in brain I-1-P levels, although we could not get conclusive data because the number of the samples was so small that the statistical analysis has not been done yet. This increase was suppressed by the pretreatment of 5HT_2 antagonist (ketanserin).
Secondly, we tried to make the rats which showed 5HT_2 receptor supersensiivity. Acute stress (immobilization stress for 1 hr) and chronic stress (immobilization for 1 hr./day for 7 days) was administered to the rats and the behavioral reoponses to the 5HT_2 agonist (DOI) were compared. As the chronic stress rats showed significant increase of head shakes comparing with the non-immobilized controls, these rats were consdered to be the model of 5HT_2 recoptor supersensitivity.
Thirdly, PME/beta was detected by in vivo ^<31>P-MRS in the model rats. We could not get the conclusion so far because the experiments are still continued and the number of the samples is too small to analyze statistically. Although further experiments should be done to obtain any conclusive findings, it became clear through this project that a non invasive methodology for monitoring changes in PI turnover would be helpful to the research of affective disorders.
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