Atomoxetine blocks motor hyperactivity in neonatal 6-hydroxydopamine-lesioned rats: implications for treatment of attention-deficit hyperactivity disorder
Atomoxetine blocks motor hyperactivity in neonatal 6-hydroxydopamine-lesioned rats: implications for treatment of attention-deficit hyperactivity disorder
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DOI：
10.1017/s1461145705005249
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发表时间：
2005-09-01
影响因子：
4.8
通讯作者：
Tarazi, FI
中科院分区：
文献类型：
--
作者：
Moran-Gates, T;Zhang, K;Tarazi, FI
我们最近报道，去甲肾上腺素（NE）、地昔帕明和尼索西汀的神经元转运的选择性抑制剂逆转了注意力缺陷多动障碍（ADHD）动物模型的运动过度活跃。在这项研究中，我们检查了托莫西汀（一种有效的新型 NE 再摄取阻滞剂）对前脑多巴胺投射出现 6-羟基多巴胺 (6-OHDA) 损伤的幼年雄性大鼠的行为影响。出生后第 5 天（PD）在地昔帕明（皮下注射 25 mg/kg）预处理后，脑池内给予 6-OHDA（100 μg），以保护去甲肾上腺素能神经元。在新环境中记录 PD 23-26 90 分钟的运动活动之前，腹腔内给予托莫西汀 (1 mg/kg)。托莫西汀极大地降低了 6-OHDA 损伤大鼠的运动过度活跃，同时在假手术对照组中表现出短暂的镇静作用。在该 ADHD 动物模型中观察到的效果与托莫西汀作为一种新型非刺激性 ADHD 治疗方法的新兴临床应用一致。
We recently reported that selective inhibitors of neuronal transport of norepinephrine (NE), desipramine and nisoxetine, reversed motor hyperactivity in an animal model of attention-deficit hyperactivity disorder (ADHD). In this study, we examined behavioural effects of atomoxetine, a potent new NE reuptake blocker, in juvenile male rats with neonatal 6-hydroxydopamine (6-OHDA) lesions of dopamine projections to the forebrain. 6-OHDA (100 mu g) was administered intracisternally on postnatal day (PD) 5 following desipramine (25 mg/kg s.c.) pretreatment to protect noradrenergic neurons. Atomoxetine (1 mg/kg) was given intraperitoneally before recording motor activity for 90 min at PD 23-26 in a novel environment. Atomoxetine greatly reduced motor hyperactivity in 6-OHDA-lesioned rats while exhibiting transient sedative effects in sham controls. The observed effects in this animal model for ADHD are consistent with the emerging clinical use of atomoxetine as a novel, non-stimulant treatment for ADHD.