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首页> 美国卫生研究院文献>Wiley-Blackwell Online Open >SERT and uncertainty: serotonin transporter expression influences information processing biases for ambiguous aversive cues in mice
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SERT and uncertainty: serotonin transporter expression influences information processing biases for ambiguous aversive cues in mice

机译：ERT和不确定性：5-羟色胺转运蛋白的表达影响小鼠歧义厌恶线索的信息处理偏差

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摘要

The long allele variant of the serotonin transporter (SERT, 5-HTT) gene-linked polymorphic region (5-HTTLPR) is associated with higher levels of 5-HTT expression and reduced risk of developing affective disorders. However, little is known about the mechanisms underlying this protective effect. One hypothesis is that 5-HTT expression influences aversive information processing, with reduced negative cognitive bias present in those with higher 5-HTT expression. Here we investigated this hypothesis using genetically-modified mice and a novel aversive learning paradigm. Mice with high levels of 5-HTT expression (5-HTT over-expressing, 5-HTTOE mice) and wild-type mice were trained to discriminate between three distinct auditory cues: one cue predicted footshock on all trials (CS+); a second cue predicted the absence of footshock (CS−); and a third cue predicted footshock on 20% of trials (CS20%), and was therefore ambiguous. Wild-type mice exhibited equivalently high levels of fear to the CS+ and CS20% and minimal fear to the CS−. In contrast, 5-HTTOE mice exhibited high levels of fear to the CS+ but minimal fear to the CS− and the CS20%. This selective reduction in fear to ambiguous aversive cues suggests that increased 5-HTT expression reduces negative cognitive bias for stimuli with uncertain outcomes.
机译：血清素转运蛋白（SERT，5-HTT）基因相关的多态性区域（5-HTTLPR）的长等位基因变异与更高水平的5-HTT表达和降低患情感障碍的风险相关。但是，对于这种保护作用的潜在机制知之甚少。一种假设是5-HTT表达会影响厌恶性信息处理，而5-HTT表达较高的人会降低负认知偏见。在这里，我们使用转基因小鼠和新型厌恶学习范例研究了这一假设。训练了具有高水平5-HTT表达的小鼠（过表达5-HTT的5-HTTOE小鼠）和野生型小鼠，以区分三种不同的听觉提示：在所有试验中，一项提示为预测的休克（CS +）；第二个提示预测没有脚电击（CS-）；第三个提示在20％的试验（CS20％）中预测会发生触电，因此模棱两可。野生型小鼠表现出对CS +和CS20％的同等程度的恐惧，对CS-的恐惧最小。相比之下，5-HTTOE小鼠对CS +表现出很高的恐惧感，但对CS-和CS20％的恐惧却很小。这种对模棱两可的厌恶线索的恐惧的选择性减少表明，增加的5-HTT表达减少了对不确定结果的刺激的负面认知偏见。

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