Behavioral responses to social stress in noradrenaline transporter knockout mice: Effects on social behavior and depression
Behavioral responses to social stress in noradrenaline transporter knockout mice: Effects on social behavior and depression
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DOI：
10.1016/s0361-9230(02)00789-x
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发表时间：
2002-07-01
影响因子：
3.8
通讯作者：
Liposits, Z
中科院分区：
文献类型：
--
作者：
Haller, J;Bakos, N;Liposits, Z
去甲肾上腺素与抑郁症的发病机制有关，去甲肾上腺素转运体(Net)是一些抗抑郁药物的靶点。因此，Net基因表达受阻的小鼠(Net-KO)似乎特别适合研究这种行为障碍。我们在Net-KO小鼠中研究了社会压力(抑郁的一个病因)和由此导致的抑郁行为之间的相互作用。社交压力是由较大的常驻小鼠的日常失败引起的，而抑郁是通过行为绝望模型来评估的。反复承受社会压力的动物体重增加减少，并逐渐从攻击性行为转变为防御性行为。后者可以被认为是一种特定情况下的类似抑郁的行为。净基因中断不能阻止在同型情况下(即，在重复应用相同的应激源期间)发生的这些变化。相比之下，应激Net-KO小鼠在行为绝望模型中表现出比应激野生型(WT)动物更多的挣扎。因此，在与慢性应激的原始原因不同的情况下进行测试的慢性应激动物中，净基因中断抑制了类似抑郁的行为。我们认为，在同型情况下，网络基因中断的行为效应被经验和学习所推翻，而在异型情况下则完全表现出来。初步地，我们的数据表明，增强的去甲肾上腺素功能并没有阻止特定情景的社会学习，但阻碍了抑郁症对异型情景的泛化。(C)2002 Elsevier Science Inc.保留所有权利。
Noradrenaline has been implicated in the pathogenesis of depression and the noradrenaline transporter (NET) is a target for some antidepressants. Therefore, mice with disrupted NET gene expression (NET-KO) appear especially suitable for studying this behavioral disorder. We have examined the interaction between social stress (an etiological factor of depression) and the resulting depressive behaviors in NET-KO mice. Social stress was induced by daily defeats from larger resident mice while depression was assessed by the behavioral despair model. Animals subjected to repeated social stress showed reduced weight gain and a gradual shift from offensive to defensive behaviors. The latter may be considered a situation-specific depressive-like behavior. NET gene disruption did not prevent these changes that developed in a homotypic situation (i.e., during the repeated application of the same stressor). In contrast, stressed NET-KO mice showed more struggling in the behavioral despair model than stressed wild type (WT) animals. Thus, NET gene disruption inhibited depression-like behavior in chronically stressed animals tested in a situation heterotypic to the original cause of chronic stress. We suggest that the behavioral effects of NET gene disruption were overruled by experience and learning in the homotypic situation but manifested fully in the heterotypic situation. Tentatively, our data suggest that enhanced noradrenergic function does not prevent situation-specific social learning but impedes the generalization of depression to heterotypic circumstances. (C) 2002 Elsevier Science Inc. All rights reserved.