Divided attention may be more important than ever to comprehend, given ubiquitous distractors in modern living. In humans, concern has been expressed about the negative impact of distraction in education, the home, and the workplace. While acetylcholine supports divided attention, in part via muscarinic receptors, little is known about the specific muscarinic subtypes that may contribute. We designed a novel, high-response rate test of auditory sustained attention, in which rats complete variable-ratio runs on one of two levers, rather than emitting a single response. By doing this, we can present a secondary visual distractor task during some trials, for which a correct nosepoke response is reinforced with a more palatable food pellet. The nonspecific muscarinic antagonist scopolamine impaired performance, and slowed and reduced lever press activity. We then explored antagonists that preferentially block the M1 and M4 subtypes, because these receptors are potential therapeutic targets for cognitive enhancers. Telenzepine, an M1-preferring antagonist, impaired divided attention performance, but not performance of the attention task without distraction. Telenzepine also had fewer nonspecific effects than scopolamine. In contrast, the M4-preferring antagonist tropicamide had no effects. Analysis of overall behavior also indicated that accuracy in the main attention task decreased as a function of engagement with the distractor task. These results implicate the M1 receptor in divided attention.

鉴于现代生活中无处不在的干扰因素，分散注意力可能比以往任何时候都更重要。在人类中，已经表达了对教育、家庭和工作场所分心的负面影响的担忧。虽然乙酰胆碱支持分散注意力，部分是通过毒蕈碱受体，但对可能起作用的特定毒蕈碱亚型知之甚少。我们设计了一种新颖的、高响应率的听觉持续注意力测试，其中大鼠在两个杠杆中的一个上完成可变比率运行，而不是发出单一响应。通过这样做，我们可以在一些试验中呈现二次视觉干扰任务，为此，正确的鼻戳反应通过更可口的食物颗粒得到加强。非特异性毒蕈碱拮抗剂东莨菪碱损害性能，并减慢和减少杠杆按压活动。然后我们探索了优先阻断 M1 和 M4 亚型的拮抗剂，因为这些受体是认知增强剂的潜在治疗靶点。Telenzepine 是 M1 偏好的拮抗剂，会损害分散注意力的表现，但不会在没有分心的情况下影响注意力任务的表现。Telenzepine 的非特异性作用也比东莨菪碱少。相比之下，M4 优先拮抗剂托吡卡胺没有效果。对整体行为的分析还表明，主要注意力任务的准确性随着干扰任务的参与而降低。这些结果暗示了 M1 受体的注意力分散。因为这些受体是认知增强剂的潜在治疗靶点。Telenzepine 是 M1 偏好的拮抗剂，会损害分散注意力的表现，但不会在没有分心的情况下影响注意力任务的表现。Telenzepine 的非特异性作用也比东莨菪碱少。相比之下，M4 优先拮抗剂托吡卡胺没有效果。对整体行为的分析还表明，主要注意力任务的准确性随着干扰任务的参与而降低。这些结果暗示了 M1 受体的注意力分散。因为这些受体是认知增强剂的潜在治疗靶点。Telenzepine 是 M1 偏好的拮抗剂，会损害分散注意力的表现，但不会在没有分心的情况下影响注意力任务的表现。Telenzepine 的非特异性作用也比东莨菪碱少。相比之下，M4 优先拮抗剂托吡卡胺没有效果。对整体行为的分析还表明，主要注意力任务的准确性随着干扰任务的参与而降低。这些结果暗示了 M1 受体的注意力分散。对整体行为的分析还表明，主要注意力任务的准确性随着干扰任务的参与而降低。这些结果暗示了 M1 受体的注意力分散。对整体行为的分析还表明，主要注意力任务的准确性随着干扰任务的参与而降低。这些结果暗示了 M1 受体的注意力分散。