Martis Lena-Sophie, Krog Simone, Tran Thao Phuong, Bouzinova Elena, Christiansen Sofie L, Møller Arne, Holmes Megan C, Wiborg Ove
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark; Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, UK.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
Physiol Behav. 2018 Feb 1;184:83-90. doi: 10.1016/j.physbeh.2017.11.010. Epub 2017 Nov 10.
Patients suffering from depression-associated cognitive impairments often recover incompletely after remission from the core symptoms of depression (lack of energy, depressed mood and anhedonia). This study aimed to set the basis for clinically relevant testing of cognitive impairments in a preclinical model of depression. Hence, we used the chronic mild stress (CMS) model of depression, which provokes the core symptom of anhedonia in a fraction of the stress exposed animals, while others remain resilient, and assessed the entire CMS groups' cognitive performance on the touchscreen operant platform. Specifically, we applied the pairwise discrimination (PD) and reversal task including a retention phase on Wistar and Long Evans controls and CMS exposed Long Evans rats. We observed differences between the albino Wistar and the pigmented Long Evans strain regarding performance in the PD and reversal task as well as in memory consolidation. CMS exposure did not alter learning and memory in the PD and reversal task, even though it altered affective behaviours in the elevated plus-maze and open field test. This is likely due to the heterogeneity of the CMS group, in which stress exposure elicited the expected range of phenotypes from anhedonic-like to resilient shown with the sucrose consumption test. Thus, our study suggests that pigmented rat strains, such as Long Evans, are superior to albino rats in the vision-based touchscreen studies. Furthermore, we propose investigation of the CMS subgroups in more complex, hippocampus-dependent tasks to refine a translational preclinical model of depression-induced cognitive impairments. Hence, this study increased awareness of strain-specific differences in touchscreen performance and added to the literature regarding the sensitivity of the PD and reversal task to stress-induced cognitive alterations.
患有与抑郁症相关的认知障碍的患者在抑郁症核心症状（缺乏精力、情绪低落和快感缺失）缓解后，往往恢复不完全。本研究旨在为抑郁症临床前模型中认知障碍的临床相关测试奠定基础。因此，我们使用了抑郁症的慢性轻度应激（CMS）模型，该模型在一部分受到应激的动物中引发快感缺失的核心症状，而其他动物则保持恢复力，并在触屏操作平台上评估了整个CMS组的认知表现。具体而言，我们对Wistar大鼠和Long Evans对照大鼠以及接受CMS处理的Long Evans大鼠应用了成对辨别（PD）和反转任务，包括一个保持阶段。我们观察到，在PD和反转任务的表现以及记忆巩固方面，白化Wistar大鼠和有色Long Evans品系之间存在差异。尽管CMS处理改变了高架十字迷宫和旷场试验中的情感行为，但在PD和反转任务中，它并未改变学习和记忆。这可能是由于CMS组的异质性，在该组中，应激暴露通过蔗糖消耗试验显示出从快感缺失样到恢复力的预期表型范围。因此，我们的研究表明，在基于视觉的触屏研究中，有色大鼠品系，如Long Evans大鼠，优于白化大鼠。此外，我们建议在更复杂的、依赖海马体的任务中研究CMS亚组，以完善抑郁症诱导的认知障碍的转化临床前模型。因此，本研究提高了对触屏表现中品系特异性差异的认识，并补充了关于PD和反转任务对应激诱导的认知改变的敏感性的文献。
