RATIONALE Tramadol is widely used for pain relief especially in seniors. However, long-term use of tramadol has serious adverse effects, including cognitive impairment. Besides its memory effects, already demonstrated in animals, a recent clinical report suggests that tramadol could also affect executive function in seniors. Several studies have hypothesized that the anti-muscarinic properties of tramadol could be responsible for the deleterious effects of tramadol on cognition. OBJECTIVES We aimed at investigating the effects of chronic administration of tramadol on cognitive flexibility in adult male mice, as assessed by a visual discrimination reversal task using a touchscreen device. The effects of tramadol were further compared to those of scopolamine, a reference muscarinic antagonist. RESULTS We found that, during the early phase of the reversal task, when cognitive flexibility is most in demand, both tramadol-treated mice (20 mg/kg, s.c., twice a day) and scopolamine-treated mice (0.5 mg/kg, s.c., twice a day) needed more correction trials and showed a higher perseveration index than saline-treated mice. Therefore, tramadol affects cognitive flexibility, and its anticholinergic properties could be at least partly involved in these deficits. CONCLUSIONS In view of these deleterious cognitive effects of tramadol, physicians should be cautious when prescribing this analgesic, especially in seniors who are more vulnerable to adverse drug events and in which alternative prescription should be preferred whenever possible.

中文翻译：

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慢性曲马多给药对小鼠认知灵活性的影响。

原理曲马多广泛用于缓解疼痛，尤其是老年人。然而，长期使用曲马多有严重的副作用，包括认知障碍。除了已经在动物身上证明的记忆效应外，最近的一份临床报告表明曲马多还可能影响老年人的执行功能。几项研究假设曲马多的抗毒蕈碱特性可能是曲马多对认知产生有害影响的原因。目标我们旨在调查长期服用曲马多对成年雄性小鼠认知灵活性的影响，通过使用触摸屏设备的视觉歧视逆转任务进行评估。曲马多的作用进一步与东莨菪碱（一种参考毒蕈碱拮抗剂）的作用进行了比较。结果我们发现，在逆转任务的早期阶段，当认知灵活性最需要时，曲马多治疗的小鼠（20 毫克/公斤，皮下，每天两次）和东莨菪碱治疗的小鼠（0.5 毫克/公斤，皮下，每天两次） ) 需要更多的矫正试验，并显示出比盐水处理的小鼠更高的坚持指数。因此，曲马多影响认知灵活性，其抗胆碱能特性至少部分与这些缺陷有关。结论鉴于曲马多的这些有害的认知影响，医生在开这种镇痛药时应谨慎，尤其是在更容易发生不良药物事件的老年人中，应尽可能选择替代处方。每天两次）和东莨菪碱处理的小鼠（0.5 毫克/千克，皮下，每天两次）需要更多的校正试验，并且显示出比盐水处理的小鼠更高的坚持指数。因此，曲马多影响认知灵活性，其抗胆碱能特性至少部分与这些缺陷有关。结论鉴于曲马多的这些有害的认知影响，医生在开这种镇痛药时应谨慎，尤其是在更容易发生不良药物事件的老年人中，应尽可能选择替代处方。每天两次）和东莨菪碱处理的小鼠（0.5 毫克/千克，皮下，每天两次）需要更多的校正试验，并且显示出比盐水处理的小鼠更高的坚持指数。因此，曲马多影响认知灵活性，其抗胆碱能特性至少部分与这些缺陷有关。结论鉴于曲马多的这些有害的认知影响，医生在开这种镇痛药时应谨慎，尤其是在更容易发生不良药物事件的老年人中，应尽可能选择替代处方。其抗胆碱能特性至少部分与这些缺陷有关。结论鉴于曲马多的这些有害的认知影响，医生在开这种镇痛药时应谨慎，尤其是在更容易发生不良药物事件的老年人中，应尽可能选择替代处方。其抗胆碱能特性至少部分与这些缺陷有关。结论鉴于曲马多的这些有害的认知影响，医生在开这种镇痛药时应谨慎，尤其是在更容易发生不良药物事件的老年人中，应尽可能选择替代处方。