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Chronic stress increases dopamine levels in hippocampal dentate gyrus and impairs spatial learning and memory in rats

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Author:: No author available

Journal Title:: Acta Physiologica Sinica

Issue:: 6

DOI:: 10.13294/j.aps.2020.0085

Key Word:: 慢性应激;空间学习和记忆;齿状回;多巴胺

Abstract：本研究旨在揭示慢性应激(chronic stress,CS)对空间学习和记忆活动过程中大鼠海马齿状回(dentate gyrus,DG)的多巴胺(dopamine,DA)水平及突触效能的影响.Sprague Dawley(SD)大鼠随机分成对照组和CS组(n = 10),CS组大鼠接受慢性温和不可预知应激原处理,对照组不给予应激处理,用酶联免疫吸附法测定大鼠血清中肾上腺素和皮质酮(corticosterone,CORT)的水平,用Morris水迷宫(Morris water maze,MWM)评估大鼠的空间学习和记忆能力;用在体生物电记录法、脑部微量透析结合高效液相色谱法检测大鼠在学习和记忆活动中DG区场兴奋性突触后电位(field excitatory postsynaptic potential,fEPSP)幅值及细胞外液中DA水平的动态变化;用免疫组织化学染色或免疫蛋白印迹法检测DA的D1受体(D1 receptor,D1R)和下游通路关键蛋白在DG区的表达变化.结果显示,CS大鼠处于应激状态,表现为血清中肾上腺素和CORT水平明显升高(P ＜0.05);CS大鼠的空间学习和记忆能力下降,其学习过程中DG区突触传递效能也显著降低,表现为MWM训练第3天时,对照组大鼠DG区的fEPSP幅值与训练前比较显著升高(P＜ 0.05),而CS组却无明显改变,与对照组比较有显著差异(P＜0.05);CS大鼠DG区的DA水平在学习的第1、2、3天均明显升高,与训练前及对照组比较均有显著差异(P ＜ 0.05);和对照组相比,CS组大鼠海马DG区的D1R表达显著上调,其下游通路中磷酸化的蛋白激酶A(protein kinase A,PKA)、cAMP反应元件结合蛋白(cyclic AMP-response element binding protein,CREB)和脑源神经营养因子(brain derived neurotrophic factor,BDNF)的表达水平显著下调(P ＜ 0.05).以上结果提示,CS可能通过影响海马DG区突触传递效能和DA水平损伤大鼠的空间学习和记忆功能.

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