Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
PLoS One. 2012;7(8):e42397. doi: 10.1371/journal.pone.0042397. Epub 2012 Aug 3.
Learning of associations between aversive stimuli and predictive cues is the basis of Pavlovian fear conditioning and is driven by a mismatch between expectation and outcome. To investigate whether serotonin modulates the formation of such aversive cue-outcome associations, we used functional magnetic resonance imaging (fMRI) and dietary tryptophan depletion to reduce brain serotonin (5-HT) levels in healthy human subjects. In a Pavlovian fear conditioning paradigm, 5-HT depleted subjects compared to a non-depleted control group exhibited attenuated autonomic responses to cues indicating the upcoming of an aversive event. These results were closely paralleled by reduced aversive learning signals in the amygdala and the orbitofrontal cortex, two prominent structures of the neural fear circuit. In agreement with current theories of serotonin as a motivational opponent system to dopamine in fear learning, our data provide first empirical evidence for a role of serotonin in representing formally derived learning signals for aversive events.
学习厌恶刺激与预测线索之间的关联是巴甫洛夫式恐惧条件反射的基础，这种关联是由期望与结果之间的不匹配所驱动的。为了研究血清素是否调节这种厌恶线索-结果关联的形成，我们使用功能性磁共振成像（fMRI）和饮食色氨酸耗竭来降低健康人类受试者的大脑血清素（5-HT）水平。在巴甫洛夫式恐惧条件反射范式中，与未耗竭组相比，5-HT 耗竭组的受试者对预示即将发生不愉快事件的线索表现出较弱的自主反应。杏仁核和眶额皮层（神经恐惧回路的两个突出结构）中的恐惧学习信号也出现了类似的减少，这与当前关于血清素作为恐惧学习中多巴胺的动机对抗系统的理论一致。我们的数据为血清素在表示对不愉快事件的正式习得信号方面的作用提供了第一个经验证据。
