多巴胺能在兴奋剂诱导的清醒中的作用。
Dopaminergic role in stimulant-induced wakefulness.
作者信息
Wisor J P, Nishino S, Sora I, Uhl G H, Mignot E, Edgar D M
机构信息
Sleep Disorders Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
出版信息
J Neurosci. 2001 Mar 1;21(5):1787-94. doi: 10.1523/JNEUROSCI.21-05-01787.2001.
Abstract
The role of dopamine in sleep regulation and in mediating the effects of wake-promoting therapeutics is controversial. In this study, polygraphic recordings and caudate microdialysate dopamine measurements in narcoleptic dogs revealed that the wake-promoting antinarcoleptic compounds modafinil and amphetamine increase extracellular dopamine in a hypocretin receptor 2-independent manner. In mice, deletion of the dopamine transporter (DAT) gene reduced non-rapid eye movement sleep time and increased wakefulness consolidation independently from locomotor effects. DAT knock-out mice were also unresponsive to the normally robust wake-promoting action of modafinil, methamphetamine, and the selective DAT blocker GBR12909 but were hypersensitive to the wake-promoting effects of caffeine. Thus, dopamine transporters play an important role in sleep regulation and are necessary for the specific wake-promoting action of amphetamines and modafinil.
摘要
多巴胺在睡眠调节以及介导促醒治疗药物的作用方面存在争议。在本研究中，对发作性睡病犬进行的多导睡眠图记录和尾状核微透析液多巴胺测量显示，促醒抗发作性睡病化合物莫达非尼和苯丙胺以一种不依赖于下丘脑分泌素受体2的方式增加细胞外多巴胺。在小鼠中，多巴胺转运体（DAT）基因的缺失减少了非快速眼动睡眠时间，并独立于运动效应增加了清醒巩固。DAT基因敲除小鼠对莫达非尼、甲基苯丙胺和选择性DAT阻滞剂GBR12909通常强大的促醒作用也无反应，但对咖啡因的促醒作用敏感。因此，多巴胺转运体在睡眠调节中起重要作用，并且是苯丙胺类药物和莫达非尼特定促醒作用所必需的。
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本文引用的文献
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Increased dopaminergic transmission mediates the wake-promoting effects of CNS stimulants.多巴胺能传递增强介导了中枢神经系统兴奋剂的促觉醒作用。
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Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation.食欲素基因敲除小鼠的发作性睡病：睡眠调节的分子遗传学
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