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5-HTT 基因型和成年期社会经历对行为特征和应激反应的调节。

Modulation of behavioural profile and stress response by 5-HTT genotype and social experience in adulthood.

机构信息

Department of Behavioural Biology, University of Münster, Badestrasse 13, Münster, Germany.

出版信息

Behav Brain Res. 2010 Feb 11;207(1):21-9. doi: 10.1016/j.bbr.2009.09.033. Epub 2009 Sep 25.

DOI:10.1016/j.bbr.2009.09.033
PMID:19782704
Abstract

Behavioural profiles can be shaped by genotype and environmental factors during early phases of life. The aim of this study was to investigate whether anxiety-like behaviour, exploration and adrenocortical stress responses can be modulated by genotype and social experiences in adulthood. Male mice lacking the serotonin transporter gene which is under scrutiny for anxiety disorders were compared with heterozygous and wildtype controls. Concerning social experiences, the males of all three genotypes were provided with a winner or a loser experience in a resident-intruder paradigm on three consecutive days. Anxiety-like behaviour and exploration were recorded in the dark-light, elevated plus-maze and open-field test. To non-invasively assess adrenocortical activity, corticosterone metabolites were determined from feces. The main findings were: Repeated social experience, irrespective of winning or losing, elevated levels of anxiety-like behaviour and decreased exploration. In losers a distinct effect of genotype occurred, with homozygous knockout males showing more anxiety-like behaviour and less exploration than the other genotypes. In winners no genotype-dependent variation was found. Genotypes did not differ in basal stress hormone secretion. There was, however, a main effect of social experience with higher activation of the stress hormone system in losers than in winners. This effect was strongest in the heterozygous genotype. In conclusion, our data show that anxiety circuits retain their plasticity throughout adulthood and can be shaped by genotype and social experiences during this phase of life. Moreover, responsiveness towards negative life experiences is influenced significantly by the 5-HTT genotype.

摘要

行为特征可以通过生命早期的基因型和环境因素来塑造。本研究旨在探讨焦虑样行为、探索和肾上腺皮质应激反应是否可以通过成年期的基因型和社会经验来调节。研究比较了缺乏血清素转运体基因的雄性小鼠(该基因是焦虑障碍的研究对象)与杂合子和野生型对照。关于社会经验,所有三种基因型的雄性在连续三天的居民入侵者范式中都有赢家或输家的经历。在黑暗-明亮、高架十字迷宫和旷场测试中记录焦虑样行为和探索。为了非侵入性地评估肾上腺皮质活性,从粪便中测定皮质酮代谢物。主要发现是:重复的社会经验,无论是赢还是输,都会增加焦虑样行为和减少探索。在输家中,出现了明显的基因型效应,纯合敲除雄性比其他基因型表现出更多的焦虑样行为和更少的探索。在赢家中,没有发现基因型依赖性的变化。基因型在基础应激激素分泌方面没有差异。然而,社会经验存在主要影响,输家中应激激素系统的激活程度高于赢家。这种影响在杂合子中最为明显。总之,我们的数据表明,焦虑回路在整个成年期保持其可塑性,并可以通过生命早期的基因型和社会经验来塑造。此外,对负面生活经历的反应能力受到 5-HTT 基因型的显著影响。

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