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

滥用精神兴奋剂，如安非他明（AMP）或甲基安非他明（MAP），可以产生精神病，类似于偏执型精神分裂症。类似地，对实验动物亚慢性施用AMP或MAP诱导行为敏化，其中在停止亚慢性处理后，可通过施用这些药物的激发剂量诱导增强的行为反应。本研究旨在探讨行为敏感化的机制，包括两个实验.研究了亚慢性MAP处理后，在稳态条件下，细胞内和细胞外介质之间Na^+梯度的调控对纹状体多巴胺（DA）流出的影响。给大鼠注射MAP或生理盐水4 mg/kg，每日1次，连续14天。最后一次注射后7天，通过纹状体中的半渗透性探针局部注入哇巴因（一种Na^+，K^+-ATP酶的选择性抑制剂）。哇巴因诱导显著更大的i ...更多信息 亚慢性MAP组纹状体灌流液中DA含量较对照组增高。利血平预处理并没有影响增强哇巴因诱导的DA流出的亚慢性MAP比MAP组。与此相反，-甲基-p-酪氨酸预处理废除哇巴因诱导的DA在两组中的流出。这些结果表明，亚慢性MAP处理促进了新合成的DA的外排，这是由哇巴因引起的细胞内外Na^+梯度的降低引起的.实验用7、14、21、28、56日龄大鼠，每天2次给予MAP 2 mg/kg，连续3d，然后再给予MAP 4 mg/kg，连续3d。根据相同的时间表，对匹配的对照大鼠给予等体积的生理盐水。MAP的挑战，给予21天后，最后一次预处理，诱导MAP预处理的大鼠细胞外DA水平的显着增加与对照组相比，只有当MAP预处理启动PND 21，28和56，但不是在年轻的大鼠。相应地，MAP诱导的刻板行为只有在PND 21、28和56开始时才显著增强，而在PND 7和14则没有。这些结果表明，MAP诱导的行为敏化和释放DA的潜在能力是建立在PND 21或周围。少

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

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。

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)。

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

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。”