Szczodry Olga, van der Staay Franz Josef, Arndt Saskia S
Division of Animal Welfare & Laboratory Animal Science, Department of Animals in Science and Society, Veterinary Faculty, Utrecht University, P.O. Box 80166, 3508TD Utrecht, The Netherlands.
Emotion and Cognition Group, Department of Farm Animal Health, Veterinary Faculty, Utrecht University, P.O. Box 80151, 3508 TD Utrecht, The Netherlands.
Behav Brain Res. 2014 Nov 1;274:307-11. doi: 10.1016/j.bbr.2014.08.036. Epub 2014 Aug 24.
To enable the development of effective treatments for dementias such as Alzheimer's disease (AD), it is important to establish valid animal models of cognitive impairments. Scopolamine is widely used to induce cognitive deficits in animal models of AD, but also causes non-cognitive side effects. We assessed whether biperiden, a selective antagonist of M1 muscarinic receptors, which are predominantly expressed in brain areas involved in cognitive processes, causes cognitive deficits without inducing peripheral side-effects. Two different doses of biperiden (3 or 10mgkg(-1)) on the acquisition of a spatial cone field task were assessed in male Lister Hooded rats. This task measures, among others, spatial working (WM) - and reference memory (RM) simultaneously. Biperiden did not impair learning of the task. The animals reached asymptotic levels for all variables except reference memory and the number of rewards collected. However, the 10mgkg(-1) dose decreased the tendency of rats to use searching strategies to solve the task and made them slower to start searching and completing the task. In conclusion, though no effects on WM and RM performance were seen, the present study cannot conclude that biperiden acts as a more selective cognition impairer than scopolamine in other rats strains and/or other doses than those tested.
为了开发针对诸如阿尔茨海默病(AD)等痴呆症的有效治疗方法,建立有效的认知障碍动物模型很重要。东莨菪碱被广泛用于在AD动物模型中诱导认知缺陷,但也会引起非认知性副作用。我们评估了比哌立登(一种主要在参与认知过程的脑区表达的M1毒蕈碱受体的选择性拮抗剂)是否会在不诱发外周副作用的情况下导致认知缺陷。在雄性利斯特戴帽大鼠中评估了两种不同剂量的比哌立登(3或10mgkg(-1))对空间锥场任务习得的影响。该任务尤其能同时测量空间工作记忆(WM)和参考记忆(RM)。比哌立登并未损害任务学习。除参考记忆和收集到的奖励数量外,动物在所有变量上都达到了渐近水平。然而,10mgkg(-1)剂量降低了大鼠使用搜索策略解决任务的倾向,使它们开始搜索和完成任务的速度变慢。总之,尽管未观察到对比哌立登对WM和RM表现有影响,但本研究不能得出结论,即比哌立登在其他大鼠品系和/或除测试剂量之外的其他剂量下,比东莨菪碱是更具选择性的认知损害剂。