Rahbarnia Arya, Abela Andrew R, Fletcher Paul J
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
J Neurochem. 2025 Jan;169(1):e16232. doi: 10.1111/jnc.16232. Epub 2024 Sep 30.
The five-choice serial reaction time task (5CSRTT) is a test of attention that provides a well-validated ancillary measure of impulsive action, measured by premature responses. The task has been adapted for mice in touchscreen operant boxes, which is thought to offer improved test-retest reliability. Few studies have assessed the long-term stability of performance, including premature responding in this version of the task. We used the touchscreen 5CSRTT to conduct longitudinal testing of stability of premature responding following repeated behavioral and pharmacological manipulations. Male C57BL/6J mice were trained on a baseline version of the 5CSRTT. They were then tested on versions of the task in which the stimulus duration was reduced, and inter-trial intervals were elongated or varied within-session. Premature responding was subsequently tested following administration of pharmacological agents known to bi-directionally affect attention and impulsive action-cocaine, atomoxetine, and yohimbine. Mice were lastly re-tested 6 months later using the 5CSRTT with elongated inter-trial intervals. A reduced stimulus duration impacted attention, with reduced accuracy and increased omissions, but had no effect on premature responding. Both elongating and varying the inter-trial interval within-session increased premature responses. Mice showed similar and stable levels of increased premature responding 6 months later. Cocaine increased premature responding, though less than previously reported in rats. Atomoxetine reduced premature responding. Yohimbine had no effect on premature responding in the baseline task but decreased premature responding when tested using an elongated inter-trial interval. Overall, these results highlight that the touch screen adaptation of the 5CSRTT is an effective method for longitudinal testing of attention and impulsive action and remains sensitive to performance changes arising from repeated pharmacological and behavioral challenges.
五选择连续反应时任务（5CSRTT）是一种注意力测试，它提供了一种经过充分验证的冲动行为辅助测量方法，通过过早反应来衡量。该任务已被改编用于触摸屏操作箱中的小鼠，据认为这提高了重测信度。很少有研究评估该任务版本中表现的长期稳定性，包括过早反应。我们使用触摸屏5CSRTT对重复行为和药物操作后过早反应的稳定性进行纵向测试。雄性C57BL/6J小鼠在5CSRTT的基线版本上进行训练。然后在刺激持续时间缩短、试间间隔延长或在实验过程中变化的任务版本上对它们进行测试。随后在给予已知会双向影响注意力和冲动行为的药物——可卡因、托莫西汀和育亨宾后测试过早反应。最后，在6个月后使用试间间隔延长的5CSRTT对小鼠进行重新测试。刺激持续时间缩短会影响注意力，准确性降低且遗漏增加，但对过早反应没有影响。在实验过程中延长和改变试间间隔都会增加过早反应。6个月后，小鼠的过早反应增加水平相似且稳定。可卡因增加了过早反应，尽管比之前在大鼠中报道的要少。托莫西汀减少了过早反应。育亨宾在基线任务中对过早反应没有影响，但在使用延长的试间间隔进行测试时会减少过早反应。总体而言，这些结果表明，5CSRTT的触摸屏改编是一种用于注意力和冲动行为纵向测试的有效方法，并且对重复药物和行为挑战引起的表现变化仍然敏感。
