Selective breeding for divergence in novelty-seeking traits: Heritability and enrichment in spontaneous anxiety-related behaviors

Selective breeding for divergence in novelty-seeking traits: Heritability and enrichment in spontaneous anxiety-related behaviors
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DOI:
10.1007/s10519-006-9058-7
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发表时间:
2006-09-01
期刊:
影响因子:
2.6
通讯作者:
Akil, Huda
Akil, Huda
中科院分区:
医学3区
文献类型:
--
作者:
Stead, John D. H.;Clinton, Sarah;Akil, Huda

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近交Sprague-Dawley大鼠根据其在新环境中的探索性运动水平可分为高反应(HR)和低反应(LR)。虽然这种追求新奇的维度最初与对药物滥用的不同脆弱性有关,但行为、神经内分泌和基因表达研究表明,这些动物之间的情绪反应存在根本差异。在这里,我们报告了第一项基于这种追求新奇的维度选择性繁殖大鼠的研究。对新奇事物的反应显然是遗传的,经过8代的选择,它们的行为会有2倍的差异。三个类焦虑行为的测试一致表明,与hr饲养的动物相比,lr饲养的大鼠的焦虑程度明显更高,并且在开放场地试验中,通过服用抗焦虑药物苯二氮卓类药物氯二氮环氧化物,这种差异被减弱。交叉培养表明,对新奇事物的反应在很大程度上不受母亲互动的影响,尽管对焦虑样行为有影响。这些选定的品系将使未来研究遗传、环境和发育变量在控制药物寻求行为、压力和情绪反应方面的相互作用成为可能。
Outbred Sprague-Dawley rats can be classified as high responders (HR) or low responders (LR) based on their levels of exploratory locomotion in a novel environment. While this novelty-seeking dimension was originally related to differential vulnerability to substance abuse, behavioral, neuroendocrine and gene expression studies suggest a fundamental difference in emotional reactivity between these animals. Here, we report the first study to selectively breed rats based on this novelty-seeking dimension. Response to novelty was clearly heritable, with a > 2-fold difference in behavior seen after eight generations of selection. Three tests of anxiety-like behavior consistently showed significantly greater anxiety in LR-bred rats compared to HR-bred animals, and this difference was diminished in the open field test by administration of the anxiolytic benzodiazepine drug, chlordiazepoxide. Cross-fostering revealed that responses to novelty were largely unaffected by maternal interactions, though there was an effect on anxiety-like behavior. These selected lines will enable future research on the interplay of genetic, environmental and developmental variables in controlling drug seeking behavior, stress and emotional reactivity.