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两种基因动物模型在焦虑和抑郁行为测试中的评估

Evaluation of two genetic animal models in behavioral tests of anxiety and depression.

作者信息

Hinojosa Fedra R, Spricigo Luiz, Izídio Geison S, Brüske Gustavo R, Lopes Douglas M, Ramos André

机构信息

Laboratório de Genética do Comportamento, Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, 88.040-900 Florianópolis, SC, Brazil.

出版信息

Behav Brain Res. 2006 Mar 15;168(1):127-36. doi: 10.1016/j.bbr.2005.10.019. Epub 2005 Dec 1.

Abstract

Anxiety- and depression-related disorders often appear associated and may be affected by common genetic factors. The inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR) and the outbred rat lines Floripa H and L, which were selectively bred for high and low locomotion in the central area of the open field (OF) test, respectively, have been proposed as experimental tools to study anxiety. The main goal of the present study was to characterize the behavior of these animals in two models of anxiety, elevated plus-maze (EPM) and OF, in two models of depression, forced swim test (FST) and tail suspension test (TST) and in their home-cages. Emotionality-related differences between LEW and SHR rats and between Floripa H and L rats were found in the EPM, OF and FST. Those lines showing low anxiety-like profiles in the EPM and OF (SHR and Floripa H) also showed low immobility in the FST. The TST failed to unveil any line differences. Factor analysis involving all tests revealed three independent factors with one of them associating anxiety-related measures from the OF and EPM to immobility in the FST. When observed in their home-cages, LEW and SHR rats showed no differences in general activity, but when acutely treated with imipramine (15mg/kg), only LEW rats were sensitive to its antidepressant effects. These results suggest the existence of a genetic link between two tests used in the screening of anxiolytic drugs and one test of antidepressant activity. Moreover, the LEW and SHR rat strains were shown to be an interesting model to study the comorbidity between anxiety- and depression-related disorders.

摘要

焦虑和抑郁相关障碍常常同时出现,且可能受共同的遗传因素影响。近交系大鼠品系刘易斯大鼠(LEW)和自发性高血压大鼠(SHR),以及远交系大鼠品系弗洛里帕H系和L系,分别因在旷场试验(OF)中央区域的高运动性和低运动性而被选择性培育,已被提议作为研究焦虑的实验工具。本研究的主要目的是在两种焦虑模型(高架十字迷宫试验(EPM)和旷场试验)、两种抑郁模型(强迫游泳试验(FST)和悬尾试验(TST))以及它们的饲养笼中对这些动物的行为进行表征。在EPM、OF和FST试验中发现了LEW和SHR大鼠之间以及弗洛里帕H系和L系大鼠之间与情绪相关的差异。那些在EPM和OF试验中表现出低焦虑样特征的品系(SHR和弗洛里帕H系)在FST试验中也表现出低不动性。TST试验未能揭示任何品系差异。涉及所有试验的因子分析揭示了三个独立因子,其中一个因子将来自OF和EPM试验的与焦虑相关的测量指标与FST试验中的不动性联系起来。当在饲养笼中观察时,LEW和SHR大鼠在一般活动方面没有差异,但当用丙咪嗪(15mg/kg)进行急性处理时,只有LEW大鼠对其抗抑郁作用敏感。这些结果表明,在用于筛选抗焦虑药物的两种试验和一种抗抑郁活性试验之间存在遗传联系。此外,LEW和SHR大鼠品系被证明是研究焦虑和抑郁相关障碍共病的一个有趣模型。

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