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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：
KUSUMI Ichiro
金额：
$ 1.92万
依托单位：
HOKKAIDO UNIVERSITY
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