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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

本实验观察了非竞争性N-甲基-D-天冬氨酸受体拮抗剂苯环利定对大鼠纹状体和额叶皮质多巴胺D-羟色胺D22-羟色胺D22-ィイ-D2和5-羟色胺-5-羟色胺-ィエ-D22A-ィイ-D2受体结合的影响。5 mg/kgPCP急性给药或3周给药对D-ィイ、D22、ィエ、D2和5-HT、ィイ、D22A、ィエ、D2受体均无明显影响。急性或8天足电击应激(1系列：2.5 mA，随机间隔30秒；平均30秒，30次)对生理盐水和五氯苯酚(5 mg/kg)处理的大鼠的D2和5-羟色胺ィイD22AィエD2受体没有显著影响。然而，应激诱导的D-ィイD22ィエD2和5-HTィイD22AィエD2受体的变化在两组之间是不同的，尽管没有显著差异。氯丙嗪与3种典型抗精神病药物(利培酮、奥氮平和培螺酮)联合治疗3周对D-ィイD22…结合的影响ィエD2和5-羟色胺ィイD22AィエD2受体分别在大鼠纹状体和额叶皮质表达。亚慢性给予氯丙嗪(10 mg/kg)和洛氮平(1 mg/kg)后，DィイD22ィエD2受体显著增加，而低剂量氯丙嗪(5 mg/kg)、丙螺酮(0.1 mg/kg)、利培酮(0.2 5 mg/kg)或奥氮平(1、2 mg/kg)则无明显增加。给予氯丙嗪(5，10 mg/kg)和奥氮平(1，2 mg/kg)3周后，5-羟色胺ィイD22AィエD2受体明显减少，而利培酮(0.25，0.5 mg/kg)或培螺酮(0.1，1 mg/kg)无明显作用。用N-乙氧基碳基-2-乙氧基-1，2-二氢喹啉测定D-ィイD22ィエD2和5-HTィイD22AィエD2受体在体内的药物占有率表明，5-HTィイD22AィエD2受体占有率高而DィイD22ィエD2受体占有率较低可能与一些非典型抗精神病药物亚慢性治疗后DィイD22ィエD2受体没有上调有关。较少