摘要
注意力缺陷和多动症(ADHD)症状的特征在于粗心和极度活跃。它是一种常见的儿童神经发育障碍,往往持续到成年。用精神振奋药物改善ADHD症状被认为是一种矛盾的镇静作用。精神兴奋药盐酸哌甲酯控制片(MPH)目前被用作治疗ADHD的一线药物。最近的研究提到注意改变多巴胺介导的神经传递多动症,特别是通过多巴胺转运蛋白(DAT)的再摄取。这种假设是由观察到的DAT基因敲除小鼠表现出的显著极度活跃所支持,这种极度活跃对急性MPH治疗敏感。但是,其他与多动症有关行为尚未完全阐明。在本研究中,我们观察到了DAT基因敲除小鼠在新环境中的梭箱回避行为和极度活跃的学习障碍。盐酸哌甲酯控释片使这些行为正常化且增加大鼠悬尾实验中的躲避行为。有趣的是,有效剂量的MPH增加前额皮质的细胞外多巴胺,而不增加纹状体的,说明在ADHD中前额多巴胺的改变重要性。运用啮齿动物模型如DAT敲除小鼠的研究可能对阐明多动症的病理生理学有用。
关键词: ADHD,多巴胺转运蛋白,额叶皮质,敲除,学习,哌醋甲酯,去甲肾上腺素转运蛋白
Current Molecular Medicine
Title:Improvement of Learning and Increase in Dopamine Level in the Frontal Cortex by Methylphenidate in Mice Lacking Dopamine Transporter
Volume: 15 Issue: 3
Author(s): Y. Takamatsu, Y. Hagino, A. Sato, T. Takahashi, S.Y. Nagasawa, Y. Kubo, M. Mizuguchi, G.R. Uhl, I. Sora and K. Ikeda
Affiliation:
关键词: ADHD,多巴胺转运蛋白,额叶皮质,敲除,学习,哌醋甲酯,去甲肾上腺素转运蛋白
摘要: The symptoms of attention-deficit/hyperactivity disorder (ADHD) are characterized by inattention and hyperactivity-impulsivity. It is a common childhood neurodevelopmental disorder that often persists into adulthood. Improvements in ADHD symptoms using psychostimulants have been recognized as a paradoxical calming effect. The psychostimulant methylphenidate (MPH) is currently used as the first-line medication for the management of ADHD. Recent studies have drawn attention to altered dopamine-mediated neurotransmission in ADHD, particularly reuptake by the dopamine transporter (DAT). This hypothesis is supported by the observation that DAT knockout mice exhibit marked hyperactivity that is responsive to acute MPH treatment. However, other behaviors relevant to ADHD have not been fully clarified. In the present study, we observed learning impairment in shuttle-box avoidance behavior together with hyperactivity in a novel environment in DAT knockout mice. Methylphenidate normalized these behaviors and enhanced escape activity in the tail suspension test. Interestingly, the effective dose of MPH increased extracellular dopamine in the prefrontal cortex but not striatum, suggesting an important role for changes in prefrontal dopamine in ADHD. Research that uses rodent models such as DAT knockout mice may be useful for elucidating the pathophysiology of ADHD.
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Y. Takamatsu, Y. Hagino, A. Sato, T. Takahashi, S.Y. Nagasawa, Y. Kubo, M. Mizuguchi, G.R. Uhl, I. Sora and K. Ikeda , Improvement of Learning and Increase in Dopamine Level in the Frontal Cortex by Methylphenidate in Mice Lacking Dopamine Transporter, Current Molecular Medicine 2015; 15 (3) . https://dx.doi.org/10.2174/1566524015666150330144018
DOI https://dx.doi.org/10.2174/1566524015666150330144018 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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