Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague 4, Czech Republic.
The Prague College of Psychosocial Studies, Hekrova 805, 149 00, Prague, Czech Republic.
Psychopharmacology (Berl). 2018 Jul;235(7):2013-2025. doi: 10.1007/s00213-018-4899-3. Epub 2018 Apr 21.
There is a persistent pressing need for valid animal models of cognitive and mnemonic disruptions (such as seen in Alzheimer's disease and other dementias) usable for preclinical research.
We have set out to test the validity of administration of biperiden, an M1-acetylcholine receptor antagonist with central selectivity, as a potential tool for generating a fast screening model of cognitive impairment, in outbred Wistar rats.
We used several variants of the Morris water maze task: (1) reversal learning, to assess cognitive flexibility, with probe trials testing memory retention; (2) delayed matching to position (DMP), to evaluate working memory; and (3) "counter-balanced acquisition," to test for possible anomalies in acquisition learning. We also included a visible platform paradigm to reveal possible sensorimotor and motivational deficits.
A significant effect of biperiden on memory acquisition and retention was found in the counter-balanced acquisition and probe trials of the counter-balanced acquisition and reversal tasks. Strikingly, a less pronounced deficit was observed in the DMP. No effects were revealed in the reversal learning task.
Based on our results, we do not recommend biperiden as a reliable tool for modeling cognitive impairment.
对于认知和记忆障碍（如阿尔茨海默病和其他痴呆症中所见）的有效动物模型，存在持续的迫切需求，可用于临床前研究。
我们旨在测试使用哌甲酯（一种具有中枢选择性的 M1-乙酰胆碱受体拮抗剂）作为生成认知障碍快速筛选模型的潜在工具的有效性，在杂交 Wistar 大鼠中。
我们使用了几种变体的 Morris 水迷宫任务：（1）反转学习，以评估认知灵活性，通过探测试验测试记忆保留；（2）延迟匹配到位置（DMP），评估工作记忆；和（3）“平衡获取”，以测试获取学习中可能存在的异常。我们还包括可见平台范式，以揭示可能存在的感觉运动和动机缺陷。
在平衡获取和反转任务的平衡获取和反转试验中，发现哌甲酯对记忆获取和保留有显著影响。值得注意的是，在 DMP 中观察到的缺陷不那么明显。在反转学习任务中未显示出任何效果。
根据我们的结果，我们不建议将哌甲酯作为建模认知障碍的可靠工具。
