ISSN 0439-755X
CN 11-1911/B

心理学报 ›› 2009, Vol. 41 ›› Issue (01): 53-61.

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  1. (1 浙江大学心理与行为科学系 ,杭州 310028)(2 杭州师范大学临床医学院,杭州 310036)(3 浙江大学医学院附属邵逸夫医院, 杭州 310016)

  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2009-01-30 发布日期:2009-01-30
  • 通讯作者: 许百华

Effects of Antidepressant on the Expression of Neuropeptide Y in Brain of a Rat Model of Depression Induced by Chronic Stress

SHEN Yue-Di;XU Bai-Hua;LIU Na;WEI Li-Li;CHEN Wei   

  1. Department of Psychology and Behavioral Sciences, School of Sciences, Zhejiang University, Hangzhou 310028, China
  • Received:1900-01-01 Revised:1900-01-01 Online:2009-01-30 Published:2009-01-30
  • Contact: XU Bai-Hua

摘要: 神经肽Y是一个多肽,广泛分布于周围和中枢神经系统,以下丘脑的浓度为高,参与机体神经内分泌、情绪、行为等的调节。 为探讨慢性应激诱导的抑郁模型小鼠脑内神经肽Y (NPY)的表达,以及抗抑郁药的作用机理,采用慢性应激与孤养方法,建立抑郁小鼠模型。用旷场行为 (Open-Field)法,观察模型组与正常对照组行为学改变方面的差异。将36 只抑郁模型小鼠随机分成盐酸氟西汀组、盐酸阿米替林组、生理盐水治疗组,并与12 只正常对照组比较。用半定量逆转录-聚合酶联反应(RTPCR) 法、细胞酶联免疫法及蛋白免疫印迹(Westernblot) 法、免疫组织化学法,比较四组小鼠下丘脑NPY 的表达。结果表明:(1)与正常组比较,抑郁模型组小鼠活动总路程与活动次数减少(p< 0.01),体重增速下降(p< 0.05)。(2)与正常组比较,抑郁模型组小鼠下丘脑NPY mRNA 表达下降(p< 0.01);经盐酸氟西汀、盐酸阿米替林治疗后,下丘脑NPY mRNA 及蛋白表达增高,与生理盐水组比较差异显著(p< 0.01)。(3) 正常组比较,生理盐水治疗组胞膜和胞质呈棕黄色染色,显示出明显的免疫组化阳性反应;经盐酸氟西汀、盐酸阿米替林治疗后,胞膜和胞质的着色与背景色接近,免疫组化呈弱阳性、阴性反应。提示抑郁模型组小鼠脑内NPY 表达水平有显著下降,使用抗抑郁药有利于提高脑内NPY mRNA 及蛋白表达,可能是此类药物产生抗抑郁效应的机制之一。

关键词: 慢性应激, 抑郁, 神经肽Y, 盐酸氟西汀, 盐酸阿米替林

Abstract: Neuropeptide Y (NPY), a conservative neuroendocrine peptides widely expressed in Peripheral and Central nervous system, is associated with depression, anxiety, and digestive disease. To study NPY expression in rat model of depression and to explore the mechanisms of the antidepressants, we developed a rat model of depression by the chronic stress exposure and isolation housing. We randomly divided 36 depressed rats into three groups (n=12) and treated them with fluoxetine-, amitriptyline- and normal saline, respectively. Behavioral changes in these rats were analyzed in an Open-Field paradigm, and compared to a control group of 12 normal rats. The expression patterns of NPY in the hypothalamus were analyzed using Reverse Transcription - Polymerase Chain Reaction (RT-PCR), Western Blot, and the Immunohistochemical assays. We made the following observations:(1) Compared with the normal rats, total traveling distance and activity frequency were reduced (p <0 .01) in the depressed rats; their weight gains were smaller (p <0 .05); and their NPY mRNA levels in the hypothalamus were also lower (p < 0.01); (2) after treatment with either fluoxetine or amytriptyline, NPY mRNA and protein levels increased in brain of depressed rats. This difference is significance when compared to the normal saline group (p< 0.01).; (3) Compared with the normal control group, cell membrane and cytoplasm were stained to brown or yellow in the normal saline-treated group, indicating a positive immunohistochemical reaction. In contrast, the cell membrane and cytoplasm were stained to a color similar to the background color in the fluoxetine- and amytriptyline-treated groups, indicating a weak or negative immunohistochemical reaction. These results suggest that the brain NPY expression is reduced in the brain of depressed rats, and that a possible mechanism of the antidepressants is via enhancing rat brain NPY expression.

Key words: Depression, Amitriptyline, Chronic stress, Fluoxetine, Neuropeptide Y