托莫西汀可减少神经激肽-1受体“敲除”小鼠的多动/冲动行为。
Atomoxetine reduces hyperactive/impulsive behaviours in neurokinin-1 receptor 'knockout' mice.
作者信息
Pillidge Katharine, Porter Ashley J, Vasili Temis, Heal David J, Stanford S Clare
机构信息
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, London WC1E 6BT, UK.
RenaSci Ltd, BioCity, Pennyfoot Street, Nottingham, NG1 1GF, UK.
出版信息
Pharmacol Biochem Behav. 2014 Dec;127:56-61. doi: 10.1016/j.pbb.2014.10.008. Epub 2014 Oct 24.
BACKGROUND
Mice with functional ablation of the neurokinin-1 receptor gene (NK1R(-/-)) display behavioural abnormalities which resemble the hyperactivity, inattention and impulsivity seen in Attention Deficit Hyperactivity Disorder (ADHD). Here, we investigated whether the established ADHD treatment, atomoxetine, alleviates these abnormalities when tested in the light/dark exploration box (LDEB) and 5-Choice Serial Reaction-Time Task (5-CSRTT).
METHODS
Separate cohorts of mice were tested in the 5-CSRTT and LDEB after treatment with no injection, vehicle or atomoxetine (5-CSRTT: 0.3, 3 or 10mg/kg; LDEB: 1, 3 or 10mg/kg).
RESULTS
Atomoxetine reduced the hyperactivity displayed by NK1R(-/-) mice in the LDEB at a dose (3mg/kg) which did not affect the locomotor activity of wildtypes. Atomoxetine (10mg/kg) also reduced impulsivity in NK1R(-/-) mice, but not wildtypes, in the 5-CSRTT. No dose of drug affected attention in either genotype.
CONCLUSIONS
This evidence that atomoxetine reduces hyperactive/impulsive behaviours in NK1R(-/-) mice consolidates the validity of using NK1R(-/-) mice in research of the aetiology and treatment of ADHD.
背景
神经激肽-1受体基因功能缺失的小鼠（NK1R(-/-)）表现出行为异常，类似于注意力缺陷多动障碍（ADHD）中的多动、注意力不集中和冲动。在此，我们研究了既定的ADHD治疗药物托莫西汀，在明暗探索箱（LDEB）和5选串行反应时任务（5-CSRTT）测试中是否能减轻这些异常。
方法
分别用无注射、赋形剂或托莫西汀（5-CSRTT：0.3、3或10mg/kg；LDEB：1、3或10mg/kg）处理小鼠队列，然后在5-CSRTT和LDEB中进行测试。
结果
托莫西汀以3mg/kg的剂量降低了NK1R(-/-)小鼠在LDEB中表现出的多动，该剂量不影响野生型小鼠的运动活性。在5-CSRTT中，托莫西汀（10mg/kg）也降低了NK1R(-/-)小鼠的冲动性，但对野生型小鼠没有影响。任何剂量的药物均未影响两种基因型小鼠的注意力。
结论
托莫西汀可降低NK1R(-/-)小鼠的多动/冲动行为，这一证据巩固了在ADHD病因学和治疗研究中使用NK1R(-/-)小鼠模型的有效性。
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