中国临床心理学杂志

青少年期创伤性应激对大鼠成年后情绪和学习记忆的影响

作者：尹世平李楚婷路翠艳雷震刘德祥江虹潘芳

分类号：R395.1

出版年,卷(期):页码：2014,22(2):197-201

摘要：

目的:研究青少年期创伤性应激经历对大鼠成年后HPA轴功能、情绪和学习记忆能力的影响。方法:健康青少年雄性Wistar大鼠随机分为对照组(control group)和应激组(stress group),每组12只。采用不可回避的足底电击建立创伤性应激模型。采用旷场实验、高架十字迷宫和水迷宫评估大鼠行为学改变;地塞米松抑制试验测试HPA功能;放射免疫法测定血浆皮质酮含量;免疫组化和Western blot检测海马促肾上腺皮质激素释放激素1型受体(CRF1)表达水平。结果:与对照组相比,应激组出现明显的焦虑样行为和对环境的探索性降低,表现为在旷场实验中,中央格停留时间和直立次数均减少(P<0.05);高架十字迷宫实验中,开放臂停留时间减少和粪粒数增加(P<0.05);学习能力降低,表现为第二天水迷宫实验逃离潜伏期显著延长(P<0.05)。应激组HPA轴功能失调,血浆皮质酮水平不被地塞米松抑制。与对照组相比,应激组大鼠海马CRF1受体表达下调(P<0.05)。结论:青少年期经历的创伤性应激导致焦虑水平升高、学习与记忆功能受损,引发HPA轴功能失调。其机制之一可能与海马CRF1表达下调有关。这可能是个体成年后更易出现应激相关的情绪与认知障碍的原因。

Objective: To investigate the effects of traumatic stress experience in early adolescence on emotion, learning and memory of adult rats. Methods: Early-adolescent male Wistar rats were randomly divided into control group and stress group. The traumatic stress animal model was produced by electric foot shock. Open field test, the elevated plus maze and Morris water maze were used to test the behavioral alterations. HPA axis reactivity and the level of plasma corticosterone were evaluated by the dexamethasone-suppression test(DST) and radioimmunoassay. Corticotropin-releasing factor receptor type-1(CRF1) expression in Hippocampus was detected using Immunohistochemistry and Western blotting. Results: The stress group exhibited more anxiety-like behaviors and impairment of learning and memory( P <0.05 respectively) by showing less rearing and less time spent in central zone in open field test; less time spent in open arms and more droppings pellets in elevated plus maze test and longer latency time to platform on day 2 in Morris water maze compared to the control group. Stress group had a dysregulation of HPA axis as plasma corticosterone could not be suppressed in DST compared with control group. CRF1 expression in Hippocampus was significantly down-regulated in the stress group( P <0.05). Conclusion: Traumatic stress in early adolescent induces anxiety and learning and memory impairment, leads to HPA axis dysregulation. Reduced CRF1 in hippocampus may underlie the dysregulated HPA axis and damaged learning and memory.

基金项目：

山东省自然科学基金(ZR2011CM015)

作者简介：

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