Study of mechanism of action of antipsychotic drugs in the animal model of schizophrenia

抗精神病药物在精神分裂症动物模型中的作用机制研究

基本信息

  • 批准号:
    09670969
  • 负责人:
  • 金额:
    $ 1.92万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1997
  • 资助国家:
    日本
  • 起止时间:
    1997 至 1999
  • 项目状态:
    已结题

项目摘要

The effect of non-competitive NMDA receptor antagonist phencyclidine (PCP) on the binding to dopamine DィイD22ィエD2 and serotonin 5-HTィイD22AィエD2 receptor was examined in the rat striatum and frontal cortex, respectively. Neither acute or 3-week treatment with 5 mg/kg PCP had any significant effect on DィイD22ィエD2 and 5-HTィイD22AィエD2 receptors. Acute or 8-day footshock stress (1 series: 2.5 mA for 30 sec, randam interval; mean 30 sec, 30 times) did not significantly affect the D2 and 5-HTィイD22AィエD2 receptors in both saline- and PCP (5 mg/kg)-treated rats. However, stress-induced changes in the DィイD22ィエD2 and 5-HTィイD22AィエD2receptors were different, although not significantly, between the two groups. It is possible that PCP treatment may influence the dopaminergic and serotonergic compensatory systems to stress.The effects of 3-week treatment with a atypical antipsychotic drug chlorpromazine and three typical antipsychotic drugs (risperidone, olanzapine and perospirone) on the binding to DィイD22 … More ィエD2 and 5-HTィイD22AィエD2 receptors were examined in the rat striatum and frontal cortex, respectively. Subchronic treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) significantly increased DィイD22ィエD2 receptors, while no increase was observed with lower dose of chlorpromazine (5 mg/kg), perospirone (0.1 mg/kg), risperidone (0.25, 0.5 mg/kg) or olanzapine (1, 2 mg/kg). On the other hand, 3-week administration of chlorpromazine (5, 10 mg/kg)and olanzapine (1, 2 mg/kg) significantly decreased 5-HTィイD22AィエD2 receptors, but risperidone (0.25, 0.5 mg/kg) or perospirone (0.1, 1 mg/kg) had no effect. The measurement of in vivo drug occupation for DィイD22ィエD2 and 5-HTィイD22AィエD2 receptors using N-ethoxycarbony1-2-ethoxy-1, 2-dihydroquinoline (EEDQ) suggested that high occupation of 5-HTィイD22AィエD2 receptors with lower DィイD22ィエD2 receptor occupancy might be involved in the absence of up-regulation of DィイD22ィエD2 receptors after subchronic treatment with some atypical antipsychotic drugs. Less
用非竞争性NMDA受体拮抗剂苯环利定(PCP)分别在大鼠纹状体和额叶皮层观察了多巴胺D受体D22和5-羟色胺(5-HT)受体D22结合的影响。以5毫克/千克五氯苯酚进行急性或为期3周的处理,对D受体D22和5-HT受体D22 A和D2受体均无任何显著影响。急性或8天的足电击应激(1系列:2.5 mA,30秒,随机间隔;平均30秒,30次)没有显着影响D2和5-HT受体D22 A受体D22在盐水和PCP(5毫克/公斤)处理的大鼠。然而,应激诱导的D-羟色胺D22受体和5-羟色胺D22 A受体的变化在两组之间是不同的,尽管不显著。PCP治疗可能影响多巴胺能和多巴胺能代偿系统对应激的反应。用非典型抗精神病药物氯丙嗪和三种典型抗精神病药物(利培酮、奥氮平和哌罗匹隆)治疗3周对D受体D22结合的影响 ...更多信息 在大鼠纹状体和额叶皮层分别检测了多巴胺D2和5-HT多巴胺D22 A受体。氯丙嗪(10 mg/kg)和哌罗匹隆(1 mg/kg)的亚慢性治疗显著增加了D受体D22,而较低剂量的氯丙嗪(5 mg/kg),哌罗匹隆(0.1 mg/kg),利培酮(0.25,0.5 mg/kg)或奥氮平(1,2 mg/kg)没有观察到增加。另一方面,氯丙嗪(5,10 mg/kg)和奥氮平(1,2 mg/kg)给药3周可显著降低5-HT受体D22 A亚型D2受体,但利培酮(0.25,0.5 mg/kg)或哌罗匹隆(0.1,1 mg/kg)无影响。使用N-乙氧羰基-2-乙氧基-1,2-二氢喹啉(EEDQ)表明,在缺乏向上-某些非典型抗精神病药物亚慢性治疗后D受体D22的调节。少

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kusumi I.: "Algorithms for the treatment of acute side effects induced by neuroleptics"Psychiat.Clin.Neurosci.. 53(suppl.). s19-s22 (1999)
Kusumi I.:“治疗精神安定药引起的急性副作用的算法”Psychiat.Clin.Neurosci.. 53(增刊)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
久住 一郎: "病態・病理-精神化学/臨床精神医学講座2精神分裂病I" 中山書店, 149-167 (1999)
久住一郎:“医疗状况/病理学 - 心理化学/临床精神病学课程 2 精神分裂症 I” 中山书店,149-167 (1999)
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
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  • 通讯作者:
久住一郎: "精神分裂病のアルゴリズム―急性の副作用"星和書店(精神分裂病と気分障害の治療手順). 179 (1998)
Ichiro Kusumi:“精神分裂症算法 - 急性副作用”Seiwa Shoten(精神分裂症和情绪障碍的治疗程序)179(1998)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Sato, M.: "Algorithm for the treatment of schizophrenia in Japan"Int. J. Psychiat. Clin. Pract.. 3. 271-276 (1999)
Sato, M.:“日本治疗精神分裂症的算法”Int。
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  • 影响因子:
    0
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Takahashi Y: "In vivo occupation of dopamine D_1,D_2 and serctonin (5HT) _<2A> receptors by sertindole in the rat brain." J.Psychiat.& Neurosci.23. 157-162 (1998)
Takahashi Y:“舍吲哚在大鼠大脑中体内占领多巴胺 D_1、D_2 和血清素 (5HT) _<2A> 受体。”
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    0
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KUSUMI Ichiro其他文献

KUSUMI Ichiro的其他文献

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{{ truncateString('KUSUMI Ichiro', 18)}}的其他基金

Systematic evaluation of endophenotypes for patients with at risk mental state and first-episode schizophrenia
精神状态高危患者和首发精神分裂症患者内表型的系统评估
  • 批准号:
    23591687
  • 财政年份:
    2011
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Neurophysiological study on cognitive pathology of depression : relevant to anterior cingulate cortex
抑郁症认知病理学的神经生理学研究:与前扣带皮层相关
  • 批准号:
    20591385
  • 财政年份:
    2008
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The role of endoplasmic reticulum stress response in the pathophysiology of bipolar disorder
内质网应激反应在双相情感障碍病理生理学中的作用
  • 批准号:
    17591192
  • 财政年份:
    2005
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular biological study on the pathophysiology of bipolar disorders
双相情感障碍病理生理学的分子生物学研究
  • 批准号:
    15591206
  • 财政年份:
    2003
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular biological study of mechanism of action of atypical antipsychotic drugs
非典型抗精神病药物作用机制的分子生物学研究
  • 批准号:
    13670978
  • 财政年份:
    2001
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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Glutamate-Energetics In Schizophrenia And Treatment Resistance
精神分裂症中的谷氨酸能量学和治疗抵抗
  • 批准号:
    MR/X021696/1
  • 财政年份:
    2024
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    $ 1.92万
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The role of nigrostriatal and striatal cell subtype signaling in behavioral impairments related to schizophrenia
黑质纹状体和纹状体细胞亚型信号传导在精神分裂症相关行为障碍中的作用
  • 批准号:
    10751224
  • 财政年份:
    2024
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    $ 1.92万
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Molecular Genetic Studies of Schizophrenia: Understanding Treatment Resistance and Outcomes to Inform Precision Psychiatry.
精神分裂症的分子遗传学研究:了解治疗耐药性和结果,为精准精神病学提供信息。
  • 批准号:
    MR/Y004094/1
  • 财政年份:
    2024
  • 资助金额:
    $ 1.92万
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Disentangling Genetic and Experiential Risk Factors for Cortical Abnormalities in a Mouse Model of Schizophrenia
解开精神分裂症小鼠模型皮质异常的遗传和经验危险因素
  • 批准号:
    MR/Y014693/1
  • 财政年份:
    2024
  • 资助金额:
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Development of a new assessment and rehabilitation strategy with a focus on executive function in schizophrenia.
制定新的评估和康复策略,重点关注精神分裂症的执行功能。
  • 批准号:
    23K10440
  • 财政年份:
    2023
  • 资助金额:
    $ 1.92万
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    Grant-in-Aid for Scientific Research (C)
Brain Metabolome Atlas in Schizophrenia Mouse Models
精神分裂症小鼠模型的脑代谢组图谱
  • 批准号:
    23H02833
  • 财政年份:
    2023
  • 资助金额:
    $ 1.92万
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Aripiprazole dose reduction in stable schizophrenia
稳定型精神分裂症阿立哌唑剂量减少
  • 批准号:
    23K06995
  • 财政年份:
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Investigation of sphingomyelin synthesis to elucidate pathophysiology and disease concept in schizophrenia.
研究鞘磷脂合成以阐明精神分裂症的病理生理学和疾病概念。
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    23K07012
  • 财政年份:
    2023
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    Grant-in-Aid for Scientific Research (C)
Functional characterization of schizophrenia rare variants using genetically engineered human iPSCs
使用基因工程人类 iPSC 进行精神分裂症罕见变异的功能表征
  • 批准号:
    10554598
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Using integrated omics to identify dysfunctional genetic mechanisms influencing schizophrenia and sleep disturbances
使用整合组学来识别影响精神分裂症和睡眠障碍的功能失调的遗传机制
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    10770880
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