| Project/Area Number |
12470192
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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 | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NISHIKAWA Toru Tokyo Medical and Dental University Professor, 大学院・医歯学総合研究科, 教授 (00198441)
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| Co-Investigator(Kenkyū-buntansha) |
KURUMAJI Akeo Tokyo Medical and Dental University Lecturer, 医学部・附属病院, 講師 (00251504)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥16,400,000 (Direct Cost: ¥16,400,000)
Fiscal Year 2001: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2000: ¥10,200,000 (Direct Cost: ¥10,200,000)
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| Keywords | Schizophrenia / Methamphetamine / Phencyclidine / Neocortex / Positive symptoms / Negative symptoms / RNA arbitrarily primed PCR / Postnatal development / 精神分裂病 / phencvclidine |
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| Research Abstract |
Schizophrenic symptoms occur after adolescence and the ability of psychotogenic drugs to induce schizophrenia-like psychosis is also age-dependent. Moreover, the behavioral responses to psychotogenic drugs in experimental animals apparently depend upon postnatal development. To obtain insight into the molecular basis of schizophrenia from a developmental point of view, we investigated in the developing rats the effects of schizophrenomimetic drugs, methamphetamine (MAP : a DA agonist which causes positive symptoms) and phencyclidine (PCP : a NMDA antagonist which causes positive and negative symptoms), on gene expression in the brain using a differential cloning technique and RT-PCR. We identified a developmentally-regulated and MAP-responsive (mrtl) or PCP-responsive (prtl) gene in the neocortex A selective D1 antagonist SCH23390 attenuated a MAP-induced upregulation of neocortical mrtlexpression, while a D2-preferring antagonist haloperidol failed to inhibit the increasing effects of PCP on prtl expression. Anti-mrt1 oligonucleotide blocked the ability of repeated MAP injection to produce reverse tolerance (behavioral sensitization : a model of the onset or relapse of positive symptoms of schizophrenia). The present data suggest that mrtl or prtl might be involved in the pathophysiology of positive or negative symptoms of schizophrenia, respectively.
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