An experimental study on relapse of schizophrenia - A biochemical study using methamphetamine psychosis

精神分裂症复发的实验研究——使用甲基苯丙胺精神病的生化研究

• 批准号: 03670564
• 负责人: AKIYAMA Kazufumi
• 金额: $ 1.28万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670564/
• 关键词: Schizophrenia; Relapse; Reverse tolerance; Methamphetamine; Dopamine; Ouabain; Postnatal development; Striatum; ウァバイン; 再燃

Abuse of psychostimulants such as amphetamine (AMP) or methamphetamine (MAP) can produce psychosis, which resembles paranoid schizophrenia. Similarly, subchronic administration of AMP or MAP to experimental animals induces behavioral sensitization, in which augmented behavioral responses can be induced by administration of challenge doses of these drugs after cessation of subchronic treatment. The present study was conducted to investigate the mechanism of behavioral sensitization, and consists of two experiments.1. The effect of manipulation of Na^+ gradient between the intracellular and extracellular media on striatal dopamine (DA) efflux under steady-state conditions after subchronic MAP treatment was investigated. Rats were injected with 4 mg/kg MAP or saline once daily for 14 days. Seven days after the last injection, ouabain, a selective inhibitor of the Na^+, K^+-ATPase, was infused locally through a semi-permeable probe in the striatum. Ouabain induced a significantly greater i … More ncrease of the DA concentrations in the striatal perfusate in the subchronic MAP than the control group. Reserpine pretreatment did not affect the enhanced ouabain-induced DA efflux in the subchronic MAP than in the MAP group. In contrast, -methyl-p-tyrosine pretreatment abolished the ouabain-induced efflux of DA in both groups. These results suggest that subchronic MAP treatment facilitates the efflux of newly synthesized DA, which is induced by the ouabain-induced decrease of the Na^+ gradient between intracellular and extracellular media.2. Experimental rats aged 7, 14, 21, 28, 56 postnatal days (PNDs) were pretreated twice daily with 2 mg/kg MAP for 3 days followed by 4 mg/kg for 3 days. Matched control rats were given equivalent volumes of saline according to the same schedule. The MAP challenge, given 21 days after the last pretreatment, induced significantly greater increases in extracellular DA levels in the MAP-pretreated rats compared with control rats only when MAP pretreatment was initiated on PNDs 21, 28 and 56, but not in younger rats. Correspondingly, MAP-induced stereotyped behavior was enhanced significantly only when MAP pretreatment was started on PNDs 21, 28 and 56, but not PNDs 7 and 14. These results suggest that MAP-induced behavioral sensitization and the underlying ability to release DA is established on or around PND 21. Less

滥用心理刺激剂，例如苯丙胺（AMP）或甲基苯丙胺（MAP）可以产生类似于偏执精神分裂症的精神病。同样，在实验动物中，亚慢性施用AMP或MAP诱导了行为敏感性，在停止下慢性治疗后，可以通过给予这些药物的挑战剂量来诱导增强的行为反应。进行了本研究以研究行为敏感性的机理，并由两个实验组成1。研究了亚慢性地图处理后，在稳态条件下，细胞内和细胞外培养基之间对纹状体多巴胺（DA）外排的操纵对纹状体多巴胺（DA）外排的影响。每天将大鼠注射4 mg/kg地图或盐水14天。上次注射七天后，通过纹状体中的半渗透探针将Na^+，K^+ATPase的选择性抑制剂Ouabain局部感染。瓦巴因（Ouabain）诱导的I…比对照组的纹状体灌注液中DA浓度更大。储层预处理并不影响亚巴氏映射中的ouabain诱导的DA外排，而不是地图组中的。相比之下， - 甲基-P-酪氨酸预处理消除了两组中DA的瓦巴因诱导的外排。这些结果表明，亚慢性地图处理促进了新合成的DA的排出，这是由ouabain诱导的细胞内和细胞外培养基之间Na^+梯度降低引起的。2。 7、14、21、28、56天（PNDS）的实验大鼠每天用2 mg/kg地图预处理3天，然后在4 mg/kg中预处理3天。根据相同的时间表，将匹配的对照大鼠赋予等效盐水。在上次预处理后21天给出的地图挑战仅在PNDS 21、28和56上启动MAP预处理时，在MAP预处理大鼠的细胞外DA水平上的增加显着增加，但在年轻大鼠中没有。相应地，仅当在PNDS 21、28和56上启动MAP预处理时，地图引起的刻板印象才能显着增强，但不是PNDS 7和14。这些结果表明，在PND 21或PND 21上建立了MAP诱导的行为敏感性以及释放DA的潜在能力。

项目成果

Kazufumi Akiyama et al.: "Taniguchi Symposia on Brain Sciences No.14 Biulugical Basis of Schizophrenic Discodess(Methamphetamine psychosis as a model of relapse of schizophrenia:A behavioral and biochemical study in the animal model)" 学会出版センタ-/S.Karger, 1

Kazufumi Akiyama等人：“谷口脑科学研讨会第14期精神分裂症Discodess的Biulugical基础（甲基苯丙胺精神病作为精神分裂症复发的模型：动物模型中的行为和生化研究）”学术出版中心/S.Karger， 1

Kazufumi AKIYAMA et al: "Methamphetamine psychosis as a model of relapse of Schizophrenia:A behavioral and biochemical study in the animal model Im:taniguchi Symposia on Brain sciemees NO14 Biological Basis of Schizophrenic Disorders" 学会出版センター/S.Karger, 1

Kazufumi AKIYAMA 等人：“甲基苯丙胺精神病作为精神分裂症复发的模型：动物模型中的行为和生化研究 Im：taniguchi Symposia on Brain scimeees NO14 Biological Basis of Schizophrenic Disorders” Gakkai Publishing Center/S.Karger，1

秋山 一文他他: "逆耐性と再発機構" 脳と精神の医学. 3. 149-161 (1992)

Kazufumi Akiyama 等人：“逆转耐受和复发机制”《脑与精神病学医学》3. 149-161 (1992)。

Akihiro KANZAKI et al.: "Subchronic methamphetamine treatment enhances Ouabain-induced Striatal dopamine effwx in vivo" Brain Research. 569. 181-188 (1992)

Akihiro KANZAKI 等人：“亚慢性甲基苯丙胺治疗可增强哇巴因诱导的体内纹状体多巴胺功效”大脑研究。

Akihiro Kanzaki et al: "Subchronic methamphetamine treatment enhances ouabain-induced striatal dopamine efflux in vivo." Brain Research. 569. 181-188 (1992)

Akihiro Kanzaki 等人：“亚慢性甲基苯丙胺治疗可增强哇巴因诱导的体内纹状体多巴胺流出。”