Fitzpatrick Ciaràn M, Maric Vojislav S, Bate Simon T, Andreasen Jesper T
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
Department of Neuroscience, Pomona College, Claremont, USA.
Neurosci Lett. 2018 Jan 1;662:351-355. doi: 10.1016/j.neulet.2017.10.058. Epub 2017 Nov 2.
Impulsivity is a characteristic of a number of neuropsychiatric disorders such as attention-deficit/hyperactivity disorder. The 5-choice serial reaction time task (5-CSRTT) is a rodent paradigm extensively used to assess attention and impulsivity. Notably, 5-CSRTT studies do not typically account for the reduction in premature responding, the measure of impulsive action, occurring upon repeated exposure to test sessions with long or variable intertrial intervals (ITIs). This present 5-CSRTT study investigated the use of variable ITIs (5, 10 or 15s) across 15 test days (4 training days followed by 1 drug test day per week for three weeks) as previous experience had shown that 4 training days would be sufficient to induce consistent premature response levels in male C57BL/6J mice. Once a steady state was achieved, the effects of dextroamphetamine (AMPH) and (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) were then assessed using a Latin-square design to determine whether pharmacological-induced impulsive actions depended on ITI length. Mice habituated to the variable ITI schedule after only 3days and showed consistently lower premature response levels until the end of the study. AMPH (p<0.05) and DOI (p<0.05) increased the percentage of premature responses at 15s ITI trials, while only DOI (p<0.05) increased impulsive action at 10s ITI trials. Additionally, DOI increased omission rates (p<0.001), mean correct latency (p<0.01), reward collection latency (p<0.001), and reduced the total attempted trials (p<0.001). In summary, we demonstrated that mice habituate to the variable ITI schedule, suggesting that using the variable ITI schedule during training allowed premature response rates to stabilize before commencing pharmacological testing. Moreover, in these habituated mice AMPH and DOI significantly enhanced impulsive action at the long ITI trials only. We propose that experimental design considerations can improve the sensitivity of the 5-CSRTT to detect pharmacologicallyinduced impulsive action.
冲动性是多种神经精神疾病的一个特征，如注意力缺陷多动障碍。五选择连续反应时任务（5-CSRTT）是一种广泛用于评估注意力和冲动性的啮齿动物范式。值得注意的是，5-CSRTT研究通常没有考虑到在重复暴露于长或可变的试验间隔（ITI）的测试环节时，冲动行为的测量指标——过早反应的减少。本5-CSRTT研究调查了在15个测试日（4个训练日，随后每周1个药物测试日，共三周）使用可变ITI（5、10或15秒）的情况，因为之前的经验表明，4个训练日足以在雄性C57BL/6J小鼠中诱导出一致的过早反应水平。一旦达到稳定状态，然后使用拉丁方设计评估右旋苯丙胺（AMPH）和（±）-2,5-二甲氧基-4-碘苯丙胺（DOI）的作用，以确定药物诱导的冲动行为是否取决于ITI长度。小鼠仅在3天后就适应了可变ITI时间表，并在研究结束前一直表现出较低的过早反应水平。AMPH（p<0.05）和DOI（p<0.05）增加了15秒ITI试验中过早反应的百分比，而只有DOI（p<0.05）增加了10秒ITI试验中的冲动行为。此外，DOI增加了遗漏率（p<0.001）、平均正确潜伏期（p<0.01）、奖励收集潜伏期（p<0.001），并减少了总尝试试验次数（p<0.001）。总之，我们证明小鼠适应了可变ITI时间表，这表明在训练期间使用可变ITI时间表可以使过早反应率在开始药物测试前稳定下来。此外，在这些适应环境的小鼠中，AMPH和DOI仅在长ITI试验中显著增强了冲动行为。我们建议，实验设计方面的考虑可以提高5-CSRTT检测药物诱导的冲动行为的敏感性。
