Rationale

Studies on the attention-deficit/hyperactivity disorder (ADHD) have concluded that the disorder might be caused by a deficit in the inhibitory control of executive functions because of dopamine hypofunction. Recently, the intranasal route has emerged as an effective alternative means for sending dopamine directly to the brain. However, whether the treatment can ameliorate the deficits of inhibitory control in ADHD remains unknown.

Objectives

Investigating the effects of acute intranasal dopamine (IN-DA) on the inhibitory control of executive functions of an ADHD rodent model.

Methods

We trained an animal model of ADHD, the spontaneously hypertensive rat (SHR), and Wistar rats as controls, in an attentional set-shifting task (ASST) in which dopamine (0.15 mg/kg, 0.3 mg/kg, or vehicle) was intranasally administered before the final test.

Results

IN-DA application dose-dependently improved the performance and reduced errors of SHR in the initial reversal learning. The effect size was comparable to that of a peripheral injection of 0.6 mg/kg methylphenidate. In control Wistar rats, the highest dose of intranasal dopamine (0.3 mg/kg) induced deficits in the reversal learning of extradimensional discriminations.

Conclusions

The findings suggest that the IN-DA treatment has potential for use in the treatment of ADHD; however, caution must be exercised when determining the dosage to be administered, because too much dopamine may have negative effects.

中文翻译：

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急性鼻内多巴胺应用抵消自发性高血压大鼠在注意力转移任务中的逆转学习缺陷

基本原理

对注意力缺陷/多动障碍 (ADHD) 的研究得出结论，该障碍可能是由于多巴胺功能减退导致执行功能的抑制控制缺陷所致。最近，鼻内途径已成为将多巴胺直接发送到大脑的有效替代方法。然而，该治疗是否可以改善 ADHD 中抑制控制的缺陷仍然未知。

目标

研究急性鼻内多巴胺 (IN-DA) 对 ADHD 啮齿动物模型执行功能的抑制控制的影响。

方法

我们在注意力转移任务 (ASST) 中训练了 ADHD 动物模型、自发性高血压大鼠 (SHR) 和作为对照的 Wistar 大鼠，其中多巴胺（0.15 毫克/千克、0.3 毫克/千克或载体）是在最终测试前鼻内给药。

结果

IN-DA 应用剂量依赖性地提高了 SHR 在初始逆向学习中的性能并减少了错误。效果大小与外周注射 0.6 mg/kg 哌甲酯的效果相当。在对照 Wistar 大鼠中，最高剂量的鼻内多巴胺 (0.3 mg/kg) 会导致异次元歧视的逆转学习缺陷。

结论

研究结果表明，IN-DA 治疗具有治疗多动症的潜力；然而，在确定给药剂量时必须谨慎行事，因为过多的多巴胺可能会产生负面影响。