| Project/Area Number |
05670810
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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 | Kobe University School of Medicine |
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Principal Investigator |
SHIRAKAWA Osamu Kobe University School of Medicine, Department of Psychiatry, Assistant Professor, 医学部・附属病院, 講師 (40243307)
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| Co-Investigator(Kenkyū-buntansha) |
NISHINO Naoki Kobe University School of Medicine, Department of Psychiatry, Assistant Professo, 医学部, 講師 (30218177)
北村 登 神戸大学, 医学部・附属病院, 医員
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | schizophrenia / phencyclidine / methanphetamine / glutamate / transporter / 動物モデル |
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| Research Abstract |
1. To study the roles of Ca^<2+>-binding proteins in the pathology of schizophrenia, we determined the acute (1h) and delayd (24h) effects of PCP (8mg/kg, s.c.) on the gene expression of NVP (neural visinin-like Ca^<2+>-binding protein) -1 in the rat brain. After 24 hours, the NVP-1 mRNA level in the nucleus accumbens showed a significant decrease of 42%.
2. To examine the possible involvement of glutamate in the pathology of schizophrenia, we studied in the discrete rat brain regions the effect of methamphetamine (MAP) and phencyclidine (PCP) treatments on GLT-1 immunoreactivities (GLT-1-IR) , one of the glutamate transporter proteins specifically expressed in the brain, by western blot analysis. Single dose of MAP (4 mg/kg, s.c.) produced no significant changes in GLT-1-IR either one hour or 24 hours after the injection. Repetitive injections of MAP (each dose of 4 mg/kg, s.c., 5 times/week for three weeks) to rats in which we confirmed development of behavioral reverse tolerance to MAP produced a significant increase in GLT-1-IR in the caudate-putamen by about 50% (p<0.05). Single dose of PCP (8mg/kg, s.c.) produced no changes in GLT-1-IR studied one hour after the injection. Whereas, 24 hr after the injection GLT-1-IR decreased significantly in the hippocampus by about 30% (p<0.005) , with no changes in immunoreactivities of glial fibrillary acidic protein (GFAP) , a cell marker for astroglia. The increased GLT-1-IR in the caudate-putamen of rats which developed reverse tolerance to MAP suggests the relation of brain region-specific changes in glutamatergic neurotransmission to vulnerability to relapse in schizophrenic patients. The delayd response of GLT-1-IR in the hippocampus to PCP treatment may well explain an involvement of hippocampal glutamatergic abnormalities in the pathophysiology ofschizophrenia as well as the time latency in the development of human PCP psychosis.
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