Talpos John C, Aerts Nancy, Fellini Laetitia, Steckler Thomas
Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Pharmacol Biochem Behav. 2014 Jul;122:97-106. doi: 10.1016/j.pbb.2014.03.014. Epub 2014 Mar 22.
The use of touch-screen equipped operant boxes is an increasingly popular approach for modeling human cognition in the rodent. However little data is currently available describing the effects of pharmacological manipulations on touch-screen based tasks. Owing to the relationship between performance on visual-spatial paired associates learning (PAL) with schizophrenia and Alzheimer's disease one task of specific interest is the touch-screen PAL task developed for rodents (J. Talpos et al., 2009). The goal of this study was to profile a range of the commonly used pharmacological models of schizophrenia and Alzheimer's disease to investigate the sensitivity of PAL to these models of disease. Male Lister hooded rats were trained on PAL until stable performance was obtained. The effects of PCP, ketamine, amphetamine, LSD, scopolamine, and biperiden (recently proposed as an alternative to scopolamine) were then tested on animals performing the PAL task. While all compounds influenced responding during PAL, only PCP and amphetamine impaired performance with minimal changes in secondary measures (response latencies, trials completed). Surprisingly ketamine did not cause a change in percent correct despite being an NMDA antagonist, indicating that not all NMDA antagonists are equal in the touch-screen platform. This finding is in agreement with existing literature showing differential effects of NMDA antagonists on a wide variety of behavioral assays include tasks of attention, memory, and cognitive flexibility (Gilmour et al., 2009; Dix et al., 2010; Smith et al., 2011). Moreover biperiden showed no benefit when compared to scopolamine, highlighting the current lack of an effective pharmacological model of cholinergic dysfunction in the touch-screen platform. These data demonstrate that performance on PAL can be disrupted by common pharmacological disease models, suggesting that PAL may have the sensitivity to serve as a translational test for the study of cognition in humans.
使用配备触摸屏的操作箱是在啮齿动物中模拟人类认知的一种越来越流行的方法。然而，目前关于药物操作对基于触摸屏任务的影响的数据很少。由于视觉空间配对联想学习（PAL）任务的表现与精神分裂症和阿尔茨海默病之间的关系，一个特别感兴趣的任务是为啮齿动物开发的触摸屏PAL任务（J. Talpos等人，2009年）。本研究的目的是剖析一系列常用的精神分裂症和阿尔茨海默病药理学模型，以研究PAL对这些疾病模型的敏感性。雄性利斯特戴帽大鼠接受PAL训练，直到获得稳定的表现。然后在执行PAL任务的动物身上测试了苯环己哌啶（PCP）、氯胺酮、苯丙胺、麦角酸二乙酰胺（LSD）、东莨菪碱和比哌立登（最近被提议作为东莨菪碱的替代品）的效果。虽然所有化合物都影响了PAL期间的反应，但只有PCP和苯丙胺损害了表现，而次要指标（反应潜伏期、完成的试验）变化最小。令人惊讶的是，尽管氯胺酮是一种N-甲基-D-天冬氨酸（NMDA）拮抗剂，但它并没有导致正确百分比的变化，这表明并非所有的NMDA拮抗剂在触摸屏平台上都是等效的。这一发现与现有文献一致，现有文献表明NMDA拮抗剂对包括注意力、记忆和认知灵活性任务在内的各种行为测定有不同的影响（吉尔摩等人，2009年；迪克斯等人，2010年；史密斯等人，2011年）。此外，与东莨菪碱相比，比哌立登没有显示出益处，这突出了目前在触摸屏平台上缺乏有效的胆碱能功能障碍药理学模型。这些数据表明，PAL任务的表现可以被常见的药理学疾病模型破坏，这表明PAL可能具有作为人类认知研究的转化测试的敏感性。
