权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Behavioral inhibition during long-term withdrawal peridos from chronic cocaine treatment

长期可卡因治疗长期戒断期间的行为抑制

基本信息

批准号：
09670991
负责人：
USHIJIMA Itsuko
金额：
$ 1.98万
依托单位：
Yamaguchi 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 1998
项目状态：
已结题

项目摘要

The role of Gi-proteins on cataleptic responses induced by SCH23390, a dopamine Di receptor antagonist, and haloperidol, a mainly dopamine D2 receptor antagonist, 20 days after chronic cocaine treatment in rats was examined by intraperitoneal or intracerebroventriculor injection (i.p. in mice and i.c.v. in rats) of pertussis toxin (PTh) or cholera toxin (CTX), which catalyzes adenosine diphosphate (ADP)-ribosylation of Gi-proteins and Gs-proteins, respectively. In rats pretreated chronically with cocaine, haloperidol (0.1 mg/kg i.p.) exerted an enhanced cataleptic response, but SCH23390 (0.1 mg/kg i.p.) produced an attenuated response at 1 day, which converted to a supernormal response, when it was administered 20 days after the last cocaine injection. The attenuated SCH23390 cataleptic response (Di receptor supersensitivity induced one day after chronic cocaine treatment), was reversed one day after PTX treatment, whereas the enhanced haloperidol catalepsy was further potentiated. The … More enhanced cataleptic responses induced by SCH23390 and haloperidol were further potentiated 20 days after PTX (0.1 IOTA g, i.c.v. in rats, and 1 IOTA i.v. in mice) and last cocaine treatment. Regarding ADP- ribosylation of Gs-protein, the enhancing effect of SCH23390 catalepsy was potentiated, but that of haloperidol catalepsy was not affected, by CTX (0.1 , IOTA g, i.c.v. in rats, and 10 IOTA g/kg i.v. in mice), which by itself was not affected. These' results suggest that the subsensitivity of postsynaptic D_1 and D_2 receptors (increased SCH23390 catalepsy) seen during long-term withdrawal periods from chronic cocaine treatment, may involve both CTX-sensitive Gs- and PTX-sensitive Gi-protein ADP-ribosylations, or Gi protein ADP-ribosylation. The enhanced SCH23390 catalepsy seen 20 days after chronic cocaine treatment was potentiated by a single administration of clozapine or risperidone, atypical neuroleptic, in dose dependent manner, but was antagonized in animals pretreated chronically with clozapine + cocaine. In contrast, the degree of enhanced SCH23390 catalepsy seen 20 days after pretreatment chronically with a combination of cocaine + risperidone was similar to that seen after chronic cocaine alone. Chronic cocaine treatment inhibited the immobility response in the forced swimming test' 1-7 days after the chronic cocaine alone, but activated 20 days later. Chronic treatment with clozapine + cocaine antagonized the enhanced immobility response seen 20 days after chronic cocaine alone. There is a relationship between the increased cataleptic responses induced by dopamine antagonists and the enhanced immobility in the forced swimming test 20 days after chronic cocaine treatment. Less

通过腹腔内或侧脑室注射，在慢性可卡因处理大鼠20天后，检测Gi蛋白对由多巴胺D1受体拮抗剂SCH 23390和主要多巴胺D2受体拮抗剂氟哌啶醇诱导的僵硬反应的作用（在小鼠中i. p.和在大鼠中i. c. v.）的百日咳毒素（PTh）或霍乱毒素（CTX），其分别催化Gi-蛋白和Gs-蛋白的腺苷二磷酸（ADP）-核糖基化。在用可卡因慢性预处理的大鼠中，氟哌啶醇（0.1 mg/kg i. p.）表现出增强的僵硬反应，但SCH 23390（0.1 mg/kg i. p.）在第1天产生减弱的反应，当在最后一次可卡因注射后20天给药时，其转变为超常反应。减弱的SCH 23390僵硬反应（慢性可卡因治疗后一天诱导的Di受体超敏性）在PTX治疗后一天逆转，而增强的氟哌啶醇僵硬症进一步增强。的 ...更多信息在PTX（大鼠中0.1IOTA g，i. c. v.，小鼠中1 IOTA i. v.）和最后一次可卡因处理后20天，SCH 23390和氟哌啶醇诱导的增强的僵硬反应进一步增强。关于GS蛋白的ADP-核糖基化，CTX（大鼠中0.1 IOTA g，i. c. v.，小鼠中10 IOTA g/kg i. v.）增强了SCH 23390僵住症的增强作用，但氟哌啶醇僵住症的增强作用不受影响，CTX本身不受影响。这些结果提示，慢性可卡因戒断期突触后D_1和D_2受体的亚敏感性（SCH 23390僵住症增加）可能与CTX敏感的Gs和PTX敏感的Gi蛋白ADP核糖基化或Gi蛋白ADP核糖基化有关。增强SCH 23390木僵症慢性可卡因治疗后20天，加强了单次给药的氯氮平或利培酮，非典型的精神抑制剂，剂量依赖性的方式，但拮抗的动物预先处理慢性氯氮平+可卡因。相比之下，在用可卡因+利培酮的组合慢性预处理后20天观察到的增强的SCH 23390僵住症的程度与单独慢性可卡因后观察到的相似。慢性可卡因治疗在单独慢性可卡因后1-7天抑制强迫游泳试验中的不动性反应，但在20天后激活。慢性治疗氯氮平+可卡因拮抗增强不动反应后20天慢性可卡因。慢性可卡因治疗后20天，多巴胺拮抗剂诱导的僵硬反应增加与强迫游泳试验中的不动性增强之间存在关系。少