Preissmann D, Dépré M, Schenk F, Gisquet-Verrier P
Institute of Psychology, University of Lausanne, CH-1005 Lausanne, Switzerland; Department of Child and Adolescent Psychiatry, University Hospital of Geneva, Geneva, Switzerland; Department of Ecology, University of Lausanne, Lausanne, Switzerland; Cognitive Science Centre, University of Neuchâtel, Espace Louis-Agassiz, 2000, Neuchâtel, Switzerland.
Institut des Neurosciences Paris-Saclay, UMR 9197/CNRS,Département Cognition & Comportement, Université Paris-Sud, Orsay F-405, France.
Brain Res. 2016 Oct 1;1648(Pt A):459-468. doi: 10.1016/j.brainres.2016.07.042. Epub 2016 Jul 30.
In this study, we investigated long-term repercussion of early glutathione deficit by l-buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of schizophrenia. BSO rats were tested through various behavioral tasks requiring animals to take into account previously delivered information. We showed that relative to controls, BSO rats (1) were less active and more anxious in an Elevated Plus Maze test, allowing us to split them into two subgroups with high and low anxiety levels; (2) demonstrated normal abilities of behavioral flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test (WCST), with even higher abilities in anxious BSO rats suggesting reduced interference of previously acquired rules; (3) did not forage normally in radial arm mazes and mainly used clockwise strategies; (4) exhibited a lack of habituation during a startle response task; and (5) showed a normal prepulse inhibition of the startle response (PPI) and a normal conditioned taste aversion (CTA). All these results indicate that early glutathione deficit provokes persistent changes in adulthood and improves the validity of this animal model of schizophrenia. They further suggest difficulties binding temporally separated events (WCST), except when the salience of this information is very strong (CTA). We propose that the transient glutathione deficit during cerebral development could alter a "cognitive binding" process in interaction with the emotional state that could possibly account for the disruption of integrative function that characterizes schizophrenia.
在本研究中，我们通过注射L-丁硫氨酸-（S，R）-亚砜亚胺（BSO）作为精神分裂症大鼠模型，研究了早期谷胱甘肽缺乏的长期影响。通过各种行为任务对BSO大鼠进行测试，这些任务要求动物考虑先前传递的信息。我们发现，相对于对照组，BSO大鼠：（1）在高架十字迷宫试验中活跃度较低且焦虑程度更高，据此我们将它们分为高焦虑水平和低焦虑水平两个亚组；（2）在经过大鼠适应性改良的威斯康星卡片分类测验（WCST）中表现出正常的行为灵活性能力，而焦虑的BSO大鼠能力甚至更高，这表明先前习得规则的干扰减少；（3）在放射状臂迷宫中觅食不正常，主要采用顺时针策略；（4）在惊吓反应任务中缺乏习惯化；（5）惊吓反应的前脉冲抑制（PPI）和条件性味觉厌恶（CTA）正常。所有这些结果表明，早期谷胱甘肽缺乏会在成年期引发持续变化，并提高了这种精神分裂症动物模型的有效性。这些结果还进一步表明，除了信息的显著性非常强时（CTA），在结合时间上分离的事件（WCST）方面存在困难。我们提出，大脑发育过程中短暂的谷胱甘肽缺乏可能会改变与情绪状态相互作用的“认知结合”过程，这可能是精神分裂症特征性整合功能破坏的原因。
