| Project/Area Number |
63480256
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Hokkaido University |
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Principal Investigator |
YAMASHITA Itaru Hokkaido University School of Medicine, Professor, 医学部, 教授 (60000923)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Shigehiro Hokkaido University School of Medicine, Instructor, 医学部, 助手 (40142731)
KOYAMA Tsukasa Hokkaido University School of Medicine, Associate Professor, 医学部, 助教授 (10113557)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1989: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Methamphetamine / Dopamine / Serotonin / In vivo microdialysis / Stress / Conditioned fear / Learned helplessness / CRF / ド-パミン / 学習性絶望 |
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| Research Abstract |
1.After repeated methamphetamine (MAP)-pretreatment, dopamine uptake sites decreased in the rat striatum. This reduction was inhibited by alpha-methyl-p-tyrosine(alpha-MPT), dopamene1 receptor antagonist SCH23390, dopamine2 receptor antagonist YM-0913EA\ : 151-2, and NMDA receptor antagonist MK-801 pretreatment. Using in vivo microdialysis method, acute MAP administration increased striatal dopamine release in a dose-dependent manner, which increase was inhibited by alpha-MPT but not reserpine. MAP-pr13EA\ : etreatment enhanced MAP-stimulated striatal dopamine release, which was further enhanced by reserpine and inhibited by alpha-MPT pretreatment. Immobilization stress-stimulated dopamine release was enhanced by repeated MAP pretreatment.
2.Learned helplessness model : Exposure to inescapable shock produced a deficit in escape-avoidance performance 24 hour later. Subchronic pretreatment with desipramine and citalopram were not effective in preventing learned helplessness.
3.Conditioned fear stress (CFS) increased plasma corticosterone and defecation and induced freezing behavior in rats. Following CFS, increased level of DOPAC, HVA and 5-HIAA were evident in the medial prefrontal cortex.
4.Acute immoblization stress did not change corticotropin-releasing factor (CRF) concentrations in nine discrete regions of the rat brain. Repeated immobilization stress increased CRF concentration only in the median eminence.
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