Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
Behav Brain Res. 2020 Jan 27;378:112234. doi: 10.1016/j.bbr.2019.112234. Epub 2019 Sep 12.
Post-stroke depression (PSD) and post-stroke anxiety (PSA) are usually undertreated and many cases may remain undiagnosed, indicating a need for a better understanding of the underlying mechanisms. Current animal models of PSD and PSA using the middle cerebral artery occlusion model may be associated with motor deficits that can interfere with behavioral tests of depression- and anxiety-like behavior. Unilateral lesions of the medial prefrontal cortex (mPFC) have been reported to induce a depression- and anxiety-like phenotype in mice. The aim of this study was to examine the effects of unilateral microinjections of the vasoconstrictor endothelin-1 (ET-1) in the mPFC alone or in combination with the nucleus accumbens (NAc) on the behavior of rats after 2 and 6 weeks. Specifically, we measured anxiety- and depressive-like behavior, locomotion, and cognition. ET-1 injections in the mPFC and NAc resulted in replicable and localized lesions. Lesions to the mPFC and NAc resulted in more time spent in the open arms of the Elevated Plus Maze compared to sham-operated animals at 2 weeks post stroke, indicating decreased anxiety. This effect did not persist until 6 weeks post injection. No differences in locomotion, cognition and depressive-like behavior were found at either time point. In summary, unilateral lesions of mPFC and NAc did not produce a reliable and persistent anxiety and depression phenotype in rats.
卒中后抑郁（PSD）和卒中后焦虑（PSA）通常治疗不足，许多病例可能未被诊断，这表明需要更好地了解潜在机制。目前使用大脑中动脉闭塞模型的 PSD 和 PSA 的动物模型可能与运动缺陷相关，这可能会干扰抑郁和焦虑样行为的行为测试。已有研究报道，内侧前额叶皮质（mPFC）的单侧损伤可诱导小鼠出现抑郁和焦虑样表型。本研究旨在研究单侧微注射血管收缩剂内皮素-1（ET-1）单独或与伏隔核（NAc）联合对卒中后 2 周和 6 周大鼠行为的影响。具体而言，我们测量了焦虑和抑郁样行为、运动和认知。mPFC 和 NAc 中的 ET-1 注射可产生可复制和局部的损伤。与假手术动物相比，mPFC 和 NAc 的损伤导致卒中后 2 周大鼠在高架十字迷宫的开放臂中花费更多时间，表明焦虑减轻。这种效应在注射后 6 周时并未持续。在任何时间点，运动、认知和抑郁样行为均无差异。总之，mPFC 和 NAc 的单侧损伤未在大鼠中产生可靠且持久的焦虑和抑郁表型。
