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新型树鼩抑郁症社会挫败模型的效度考察
其他题名The validity of a new social defeat model of depression in tree shrew
祁可可
学位类型博士
导师隋南
2014-05
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业心理学
关键词抑郁症 社会挫败 表面效度 预测效度 结构效度
摘要目前,抑郁症研究领域正面临巨大挑战,这主要体现在对于抑郁症的病因病理机制并不完全清楚、基于啮齿类动物模型研发的抗抑郁症药物临床疗效不佳等。缺乏高效度的动物模型可能是导致这一现状的重要原因。来自进化研究的证据提示,树鼩属灵长类近缘的一种小型动物,具有较为发达的神经系统和与人类相似的应激系统,因而可能成为创制精神疾病行为模型的较佳选择。已有的研究表明,树鼩社会挫败模型可能具有比啮齿类更好的表面效度、预测效度及结构效度。由于树鼩与人类的近缘关系,对其抑郁行为的脑机制研究或药物评价可能更具潜在价值。但是,该模型只能比较片面地反应树鼩长期经历社会挫败后出现的睡眠障碍、修饰及领地标记行为减少等症状,不能模拟快感缺失、动机缺乏、兴趣减退及社交缺乏等抑郁症的核心症状。因此,根据动物的行为特点,创建能够模拟抑郁症的核心症状的树鼩抑郁症模型才能取得更好的研究成果。
本研究首先采用成年雄性树鼩争夺有限的领地及食物作为树鼩社会挫败模型的输入刺激,采用糖水偏爱测试、觅食动机测试、新颖寻求测试及社会交往测试等输出反应来模拟抑郁症的快感缺失、动机缺乏、兴趣下降及社交缺乏等抑郁症的核心症状。结果发现,在经历四周社会挫败之后, 树鼩出现了觅食动机下降、活动性降低、对新颖物体的兴趣减退及社交缺乏等症状,并且在应激停止后可以维持一周。 但是,经历社会挫败后树鼩的糖水偏爱程度并未下降。 这些结果表明,树鼩社会挫败模型具有较高的表面效度。为了考察该模型的预测效度,我们采用经典抗抑郁药——氯丙咪嗪给予经历社会挫败的树鼩四周的抗抑郁治疗,结果发现药物处理能够在一定程度上逆转经历社会挫败造成的树鼩自发活动量下降、在睡盒内停留时间增长、在新颖寻求测试中运动量降低、在社会交往测试中运动量降低及在社交区域停留时间减少等症状。但是,药物处理并不能逆转社会挫败造成的觅食动机下降。并且,与临床上相似的是,氯丙咪嗪的起效时间约需 2-4周。以上结果表明,树鼩的社会挫败模型就有较高的预测效度。
综上所述,本实验创建的新型树鼩社会挫败模型具有较高的表面效度、预测效度和结构效度,可能在抑郁症脑机制研究及未来的新药开发中发挥重要作用。
其他摘要At present, the study of depression is facing enormous challenge, which is mainly because that little is known about the pathological mechanism of depression  and the poor effect of antidepressants developed based on rodent models. While rodent models are commonly used, the tree shrew shows promise for modeling depression. Studies of tree shrews demonstrate an  evolutionary relationship to primates,  a highly developed nervous  system and a more  similar stress system to human. Previous evidence showed that the social defeat paradigm in the tree shrew may have relatively higher face, predictive and construct validities.  Underscored by a  phylogenetic  relationship to humans,  tree shrew model  of depression may provide a more  clinically-relevant approach for studying the neuro-mechanisms of depression and screening antidepressants. But he previous model did not mimic the depression’s core symptoms, like anhedonia, lack of motivation, lack of interest and lack of social interaction. 
In this study, we used two adult male tree shrews’  fight for limited territory and food  as the input stimulus,  and the sucrose preference test, the self-administration for food test, the novelty-seeking test and the social interaction test as the output response for our new social defeat model in tree shrews. The results showed that, tree shrews’ motivation for food, locomotion, interest of novelty-seeking and social interaction behavior significantly decreased after four weeks’ social defeat. But their preference for sucrose was not affected. These results indicate  that the social defeat model in tree shrew is of high face validity. Then we used clomipramine to test the predictive validity of the model. The results showed that defeated tree shrews’  locomotion, interest of novelty-seeking and social interaction behavior significantly increased after four weeks’  clomipramine treatment. But the clomipramine treatment had no effect on the decrease of the defeated tree shrews’ motivation for food. These results demonstrate that the social defeat model in tree shrew is of high predictive validity.
In  conclusion, the new social defeat model in tree shrew that we built up may have high face, predictive and construct validity. And it may play an important role in the future study of depression.
学科领域医学心理学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/19646
专题健康与遗传心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
GB/T 7714
祁可可. 新型树鼩抑郁症社会挫败模型的效度考察[D]. 北京. 中国科学院研究生院,2014.
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