| Project/Area Number |
14370287
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KOYAMA Tsukasa Hokkaido Univ., Grad.School of medicine, Professor, 大学院・医学研究科, 教授 (10113557)
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| Co-Investigator(Kenkyū-buntansha) |
KUSUMI Ichirou Hokkaido Univ Hospital, Lecturer, 病院・講師 (30250426)
ABEKAWA Tomihiro Hokkaido Univ Hospital, Assistant Professor, 病院・助手 (80301901)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | schizophrenia / cognitive dysfunction / atypical antipsychotics / prefrontal cortex / 統合失調症 / 治療抵抗性 / 病態モデル / フェンサイクリジン / 認知機能障害 / 前頭葉 |
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| Research Abstract |
Clarifying the pathogenesis and the mechanism for the treatment of cognitive dysfunction of schizophrenia is important, because this dysfunction induces serious social dysfunction in patients with schizophrenia.
Phencyclidine-induced increases in glutamate levels in the prefrontal cortex and hyperlocomotion were blocked by 5-HT2A receptor antagonist, an atypical antipsychotic, dozapine. Lesioning the mediodortsal thalamus, which projects the glutamatengic neuronal terminals to the prefrontal cortex, enhanced the behavioral and neurochemical changes of NMDA receptor antagonist, MK-801. Chronic administration of an another atypical antipsychotic, olanzapine increased protein level of dopamine D1 receptors in the prefrontal cortex, enhanced working memory of rats.
Therefore, atypical antipsychotics, which can enhance the function of NMDA receptor and dopamine D1 receptor in the prefrontal cortex, may have a potential for improving the cognitive dysfunction of schizophrenia.
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