Behavioral sensitization and alteration in monoamine metabolism in mice after single versus repeated methamphetamine administration
Behavioral sensitization and alteration in monoamine metabolism in mice after single versus repeated methamphetamine administration
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DOI：
10.1016/s0014-2999(03)02015-6
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发表时间：
2003-08-01
影响因子：
5
通讯作者：
Takemura, M
中科院分区：
文献类型：
--
作者：
Kitanaka, N;Kitanaka, J;Takemura, M
为了解决单胺能神经元系统在小鼠单次和重复给药甲基苯丙胺后的功能改变，我们检查了组织中的单胺及其代谢产物的含量，除了运动活动水平运动和饲养测量估计。在雄性ICR小鼠中，重复给药方案（每天一次腹膜内给予1.0 mg/kg甲基苯丙胺，连续5天）在试验第4天诱导了具有平台水平的过度运动。对药物的初始行为反应（注射后5分钟内）似乎包括情境依赖性敏化。初始重复治疗方案后的小鼠在最后一次注射后5天（试验第11天）对相同剂量的甲基苯丙胺表现出行为敏化。在试验第11天，药物激发后的前150分钟，但夜间行为（在黑暗时间）没有显著增强。单次和重复给药甲基苯丙胺后，小鼠纹状体+纹状体中L-二羟基苯丙氨酸含量和3，4-二羟基苯乙酸与多巴胺的比值明显降低。至于5-羟色胺代谢，5-羟基吲哚乙酸与5-羟色胺的比率在单次给药甲基苯丙胺后显著增加，尽管在重复给药甲基苯丙胺后降低。重复或单次甲基苯丙胺处理后，小鼠纹状体+丘脑或丘脑+下丘脑中的去甲肾上腺素代谢（3-甲氧基-4-羟基苯乙二醇与去甲肾上腺素的比例）未受到影响。这些结果表明，多巴胺能和多巴胺能神经元的活动发生了变化，在发展的行为敏化。3-甲氧基酪胺与多巴胺的比例不受影响，表明甲基苯丙胺治疗选择性抑制多巴胺失活的单胺氧化酶途径。(C)2003 Elsevier B. V.保留所有权利。
To address the functional alterations of monoaminergic neuronal systems in mice after single and repeated administration of methamphetamine, we examined the tissue contents of monoamines and their metabolites in addition to locomotor activity estimated by horizontal locomotion and rearing measurements. In male ICR mice, the repeated treatment regimen (intraperitoneal administration of 1.0 mg/kg methamphetamine once per day for five consecutive days) induced hyperlocomotion with a plateau level on test day 4. The initial behavioral response (within 5 min after injection) to the drug appeared to include context-dependent sensitization. Mice after the initial repeated treatment regimen showed behavioral sensitization to the same dose of methamphetamine 5 days after the final injection (test day 11). On test day 11, the first 150 min, but not the nocturnal behavior (during the dark hours), were significantly enhanced after the drug challenge. A marked reduction of the content of L-dihydroxyphenylalanine and the ratio of 3,4-dihydroxyphenylacetic acid to dopamine was observed in the striatum + accumbens of mice after single and repeated administration of methamphetamine. As for serotonin metabolism, the ratio of 5-hydroxyindolacetic acid to serotonin significantly increased in mice after single administration of methamphetamine, although it decreased in mice after repeated administration of methamphetamine. Norepinephrine metabolism (the ratio of 3-methoxy-4-hydroxyphenylglycol to norepinephrine) was not affected in the striatum + accumbens or thalamus + hypothalamus of the mice after repeated or single methamphetamine treatment. These results suggest that dopaminergic and serotonergic neuronal activities were altered during the development of behavioral sensitization. The ratio of 3-methoxytyramine to dopamine was not affected, suggesting that the methamphetamine treatment selectively inhibited the monoamine oxidase pathway for dopamine inactivation. (C) 2003 Elsevier B.V. All rights reserved.