两种慢性应激诱导的抑郁模型大鼠前额叶认知功能的比较研究

摘要

目的 本研究旨在比较两种慢性应激诱导的抑郁模型大鼠前额叶介导的认知灵活性损伤特征.方法 分别给予应激组大鼠(n=8只/组)两周慢性不可预期性应激(chronic unpredictable stress,CUS)或社会挫败(social defeat,SD)应激.应激结束后采用糖水偏好测试检测快感缺失(一种典型抑郁样行为),采用注意定势转移任务(attentional set-shifting task,AST)检测认知灵活性改变,主要包括逆反学习(reversal learning,REL)和外维度定势转移(extra-dimensional set-shifting,EDS)能力.结果 与相应对照组相比,CUS组大鼠的糖水消耗量降低[(7.24±1.64)vs (13.83±1.50),P＜0.05].SD组大鼠的糖水消耗量和糖水偏好指数较相应对照组降低[(4.28±1.96) vs (13.17±2.79),P＜ 0.01; (27.96±11.64)vs(82.97±16.13),P＜0.05].在AST测试中,CUS诱导以EDS损害为特征的认知灵活性缺失,表现在CUS组大鼠在EDS阶段的训练达标次数较相应对照组增加[(15.57±1.53)vs(10.50±1.41),P＜0.05],而社会挫败应激诱导以REL和EDS损害为特征的认知灵活性缺失,表现在SD组大鼠在REL和EDS阶段的训练达标次数均较相应对照组增加[REL:(17.30±0.76)vs (14.00±0.97),P＜0.01);EDS:(15.80±1.72) vs (9.33±0.80),P＜0.01].结论 慢性不可预期性应激和社会挫败应激诱导的抑郁模型大鼠表现出认知灵活性不同成分的损害,为进一步研究抑郁症不同认知表型障碍的神经生物学机理提供了实验基础.%Objective This study aims to characterize the features of cognitive impairment in two different models in rats. Methods Male Wistar rats underwent 2-week chronic unpredictable stress (CUS) or social defeat (SD). Sucrose preference test and attentional set shifting task (AST) were used to examine anhedonia (a core symptom of depression) and the different components of cognitive flexibility including reversal learning (REL) and extra-dimensional shifting (EDS) following the stress. Results Both CUS and SD induced a significant decrease in sucrose consumption [CUS:(7.24 ± 1.64) vs (13.83 ± 1.50), P＜ 0.05; SD: (4.28 ± 1.96) vs (13.17 ± 2.79), P＜ 0.01] and/or sucrose preference index [SD: (27.96 ± 11.64) vs (82.97 ± 16.13), P ＜ 0.05], suggesting a depressive state of anhedonia induced by chronic stress. In AST test, CUS induced the deficit of cognitive flexibility as characterized by the impairment of EDS. Rats in stress group showed an increase in the trials of criterion in EDS stage compared with corresponding controls. On the contrast, SD induced the deficit of cognitive flexibility as characterized by the impairment of both REL and EDS. Stressed rats had much more trials of criterion in REL and EDS stages compared with corresponding controls [REL: (17.30 ± 0.76) vs (14.00 ± 0.97),P ＜ 0.01); EDS: (15.80 ± 1.72) vs (9.33 ± 0.80),P ＜ 0.01]. Conclusions Both CUS and SD can induce the typical depression-like behavior, anhedonia. However, CUS and SD exerted differential effects on the different components of cognitive flexibility, suggesting that CUS and SD might be used to study neurobiological mechanisms underlying the deficits of different cognitive phe-notypes in animal model of depression.