Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Synaptic Transmission In Vivo, H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Denmark.
Psychopharmacology (Berl). 2019 Jun;236(6):1839-1851. doi: 10.1007/s00213-019-5167-x. Epub 2019 Jan 17.
The rodent Continuous Performance Test (rCPT) is a novel rodent paradigm to assess attention and impulsivity that resembles the human CPT. This task measures the rodents' ability to discriminate between target and non-target stimuli. The effect of attention-deficit/hyperactivity disorder (ADHD) medication on rCPT performance in mice remains to be fully characterized.
To investigate the predictive validity of the mouse rCPT by studying the effects of ADHD medication methylphenidate, atomoxetine, amphetamine, guanfacine, and modafinil in four behavioral subgroups based on performance and impulsivity levels.
Two cohorts of male C57BL/6J mice were used, and the effect of treatment was tested in a variable stimulus duration probe. Performance and impulsive subgroups were made based on discriminability and percentage premature responses, respectively.
Methylphenidate, atomoxetine, and amphetamine improved performance in the low-performing animals, with no effect in the high-performers. These improvements were a result of increased hit rate and/or decreased false-alarm rate. Furthermore, these drugs decreased percentage premature responses in the high-impulsive group. Methylphenidate, guanfacine, and modafinil increased premature responses in the low-impulsive group. Modafinil impaired performance in the high-performers by increasing false-alarm rate.
The effect of ADHD treatment was dependent on baseline, as seen by increases in performance for the low-performers and decreases in impulsivity for the high-impulsive animals. These results agree with clinical data and may support the inverted U-shaped arousal-performance theory. The rCPT combined with behavioral separation into subgroups has high predictive validity, and our study is a step forward towards establishing the clinical translatability of the rCPT.
啮齿动物连续性能测试（rCPT）是一种新颖的啮齿动物范式，用于评估注意力和冲动性，类似于人类的 CPT。该任务衡量啮齿动物区分目标和非目标刺激的能力。注意力缺陷多动障碍（ADHD）药物对小鼠 rCPT 性能的影响仍有待充分描述。
通过研究 ADHD 药物哌醋甲酯、阿托西汀、安非他命、胍法辛和莫达非尼在基于表现和冲动水平的四个行为亚组中的作用，来研究小鼠 rCPT 的预测有效性。
使用了两批雄性 C57BL/6J 小鼠，并用可变刺激持续时间探测来测试治疗效果。根据辨别力和过早反应的百分比，分别制作了表现和冲动亚组。
哌醋甲酯、阿托西汀和安非他命改善了低表现动物的表现，对高表现者没有影响。这些改善是由于提高了命中率和/或降低了错误警报率。此外，这些药物降低了高冲动组的过早反应百分比。哌醋甲酯、胍法辛和莫达非尼增加了低冲动组的过早反应。莫达非尼通过增加错误警报率来损害高表现者的表现。
正如临床数据所表明的那样，ADHD 治疗的效果取决于基线，表现差的动物表现提高，高冲动的动物冲动性降低。这些结果与临床数据一致，并可能支持兴奋度-表现倒 U 型理论。rCPT 结合行为分离成亚组具有很高的预测有效性，我们的研究朝着确立 rCPT 的临床可翻译性迈出了一步。
