Differences in the performance of NK1R-/- ('knockout') and wildtype mice in the 5‑Choice Continuous Performance Test.
Differences in the performance of NK1R-/- ('knockout') and wildtype mice in the 5‑Choice Continuous Performance Test.
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DOI：
10.1016/j.bbr.2015.10.045
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发表时间：
2016-02-01
影响因子：
2.7
通讯作者：
Young JW
中科院分区：
文献类型：
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作者：
Porter AJ;Pillidge K;Stanford SC;Young JW
我们在五项选择连续性能测试中比较了 NK1R−/− 小鼠和野生型小鼠的行为。 NK1R−/− 小鼠在此测试中没有表现出过度的冲动（过早反应或误报）。 NK1R−/− 小鼠表现出过度的坚持，这在 ADHD 中很常见。研究结果指出 ADHD 患者的行为表型存在 TACR1 基因多态性。在五项选择系列反应时间测试 (5-CSRTT) 中，与野生型相比，缺乏功能性 NK1（P 物质偏好）受体的小鼠通常表现出过度注意力不集中（遗漏错误）和冲动（过早反应）。这些异常行为类似于患有注意力缺陷多动障碍 (ADHD) 的人类的行为。在这里，我们使用 5 选择连续性能测试 (5C-CPT) 来确定 NK1R−/− 小鼠是否也表现出过多的误报（对“不进行”信号的不当反应），这是另一种形式的冲动行为。 NK1R−/− 小鼠比野生型小鼠完成了更多的试验，证实了它们学习和执行任务的能力。在训练的第一阶段开始时，但不是随后，它们也比野生型获得了更多的过早反应。当第一次测试小鼠时，NK1R−/− 小鼠的误报和过早反应均不高于野生型小鼠，但与 5-CSRTT 一样，后者的行为强烈依赖于一天中的时间。 NK1R−/− 小鼠在 5C-CPT 的所有阶段都表现出过度的坚持。这种行为被认为反映了强迫性检查，这在多动症患者中很常见。这些发现指出了 5-CSRTT 和 5C-CPT 方案的差异，这对于区分 NK1R−/− 小鼠的认知表现和反应控制与其野生型不同的原因可能很重要。结果进一步预测，与其他受试者组相比，携带 TACR1 基因（人类 Nk1r 基因）多态性的 ADHD 患者在连续表现测试中会表现出更多的毅力，但不会出现误报。
We compared the behaviour of NK1R−/− mice and wildtypes in the 5-Choice Continuous Performance Test. NK1R−/− mice did not express excess impulsivity (premature response or false alarms) in this test. NK1R−/− mice expressed excessive perseveration, which is common in ADHD. The findings point to a behavioural phenotype for ADHD patients with polymorphism of the TACR1 gene. Mice lacking functional NK1 (substance P-preferring) receptors typically display excessive inattentiveness (omission errors) and impulsivity (premature responses) when compared with wildtypes in the 5-Choice Serial Reaction-Time Test (5-CSRTT). These abnormal behaviours are analogous to those seen in humans suffering from Attention Deficit Hyperactivity Disorder (ADHD). Here we used the 5-Choice Continuous‑Performance Test (5C-CPT) to ascertain whether NK1R−/− mice also display excessive false alarms (an inappropriate response to a ‘no-go’ signal), which is another form of impulsive behaviour. NK1R−/− mice completed more trials than wildtypes, confirming their ability to learn and carry out the task. At the start of Stage 1 of training, but not subsequently, they also scored more premature responses than wildtypes. When the mice were tested for the first time, neither false alarms nor premature responses was higher in NK1R−/− mice than wildtypes but, as in the 5-CSRTT, the latter behaviour was strongly dependent on time of day. NK1R−/− mice expressed excessive perseveration during all stages of the 5C-CPT. This behaviour is thought to reflect compulsive checking, which is common in ADHD patients. These findings point to differences in the 5-CSRTT and 5C-CPT protocols that could be important for distinguishing why the cognitive performance and response control of NK1R−/− mice differs from their wildtypes. The results further lead to the prediction that ADHD patients with polymorphism of the TACR1 gene (the human equivalent of Nk1r) would express more perseveration, but not false alarms, in Continuous Performance Tests when compared with other groups of subjects.