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An animal model of attention deficit/hyperactivity disorder: A pharmacological perspective

机译：注意缺陷/多动障碍的动物模型：药理学角度

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摘要

Attention-deficit/hyperactivity disorder (AD/HD) is an early-onset neuropsychiatric disorder in children, symptomatically characterized by inattention and/or hyperactivity/impulsivity. Methylphenidate is commonly prescribed in the treatment of AD/HD. We have previously proposed male adolescent stroke-prone spontaneously hypertensive rats (SHRSP/Ezo) as an appropriate animal model of AD/HD, based on the symptomatic features. Male adolescent SHRSP/Ezo showed 1) attentional dysfunction (Y-maze test and 5-choice serial reaction time task), 2) hyperactivity (open-field test) and 3) impulsive behaviors based on low level of anxiety (elevated plus-maze test) as compared with genetic control Wistar-Kyoto rats. Interestingly, male but not female SHRSP/Ezo exhibited the attentional dysfunction, indicating the gender difference. SHRSP/Ezo also exerted the cortical hypoperfusion, as reported in AD/HD patients. Furthermore, angiogenic signaling molecules via VEGF/its receptors were down-regulated in the prefrontal cortex of SHRSP/Ezo. Those aberrant behaviors in SHRSP/Ezo, except for impulsivity, were ameliorated by clinical doses of methylphenidate. Attentional dysfunction in SHRSP/Ezo was also improved by atomoxetine and nicotinic agonists in the Y-maze test. Moreover, atypical antipsychotics (risperidone and olanzapine) and mood stabilizer (carbamazepine) ameliorated impulsive behaviors of SHRSP/Ezo in the elevated plus-maze test. Thus, the investigation in male adolescent SHRSP/Ezo might provide a breakthrough for exploring the pathogenesis and a novel insight for developing therapeutic agents for AD/HD.
机译：注意缺陷/多动障碍（AD / HD）是儿童的一种早发性神经精神障碍，其症状为注意力不集中和/或活动过度/冲动。在AD / HD的治疗中通常开处方哌醋甲酯。根据症状特征，我们先前曾提出雄性青少年中风倾向性自发性高血压大鼠（SHRSP / Ezo）作为AD / HD的适当动物模型。男性青少年SHRSP / Ezo表现为1）注意功能障碍（Y迷宫测试和5选择序列反应时间任务），2）多动症（开放视野测试）和3）基于低水平焦虑的冲动行为（正迷宫增强）测试）与遗传对照Wistar-Kyoto大鼠相比。有趣的是，男性而非女性SHRSP / Ezo表现出注意功能障碍，表明性别差异。正如AD / HD患者中报道的那样，SHRSP / Ezo还发挥了皮质灌注不足的作用。此外，在SHRSP / Ezo的前额叶皮层中，通过VEGF /受体的血管生成信号分子被下调。除冲动性外，SHRSP / Ezo中的异常行为可通过临床剂量的哌醋甲酯得到改善。在Y迷宫测试中，阿托西汀和烟碱激动剂也改善了SHRSP / Ezo的注意功能障碍。此外，非典型抗精神病药（利培酮和奥氮平）和情绪稳定剂（卡马西平）改善了高迷宫试验中SHRSP / Ezo的冲动行为。因此，对男性青少年SHRSP / Ezo的研究可能会为探索发病机理提供突破，并为开发AD / HD治疗剂提供新的见解。

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  • 来源
    《Experimental Animals》 |2008年第3supa期|p.12|共1页
  • 作者

    Mitsuhiro Yoshioka;

  • 作者单位

    Department of Neuropharmacology, Hokkaido University Graduate School of Medicine;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 动物学;
  • 关键词

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