Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, United Kingdom.
J Neurosci. 2013 Aug 7;33(32):12982-6. doi: 10.1523/JNEUROSCI.5587-12.2013.
Trait sensation-seeking, defined as a need for varied, complex, and intense sensations, represents a relatively underexplored hedonic drive in human behavioral neuroscience research. It is related to increased risk for a range of behaviors including substance use, gambling, and risky sexual practice. Individual differences in self-reported sensation-seeking have been linked to brain dopamine function, particularly at D2-like receptors, but so far no causal evidence exists for a role of dopamine in sensation-seeking behavior in humans. Here, we investigated the effects of the selective D2/D3 agonist cabergoline on performance of a probabilistic risky choice task in healthy humans using a sensitive within-subject, placebo-controlled design. Cabergoline significantly influenced the way participants combined different explicit signals regarding probability and loss when choosing between response options associated with uncertain outcomes. Importantly, these effects were strongly dependent on baseline sensation-seeking score. Overall, cabergoline increased sensitivity of choice to information about probability of winning; while decreasing discrimination according to magnitude of potential losses associated with different options. The largest effects of the drug were observed in participants with lower sensation-seeking scores. These findings provide evidence that risk-taking behavior in humans can be directly manipulated by a dopaminergic drug, but that the effectiveness of such a manipulation depends on baseline differences in sensation-seeking trait. This emphasizes the importance of considering individual differences when investigating manipulation of risky decision-making, and may have relevance for the development of pharmacotherapies for disorders involving excessive risk-taking in humans, such as pathological gambling.
特质寻求刺激，定义为对多样化、复杂和强烈感觉的需求，代表了人类行为神经科学研究中相对未被充分探索的享乐驱动。它与一系列行为的风险增加有关，包括物质使用、赌博和危险的性行为。自我报告的寻求刺激的个体差异与大脑多巴胺功能有关，特别是 D2 样受体，但迄今为止，没有因果证据表明多巴胺在人类寻求刺激行为中的作用。在这里，我们使用敏感的个体内、安慰剂对照设计，研究了选择性 D2/D3 激动剂卡麦角林对健康人类进行概率风险选择任务表现的影响。卡麦角林显著影响了参与者在与不确定结果相关的反应选项之间进行选择时结合不同明确概率和损失信号的方式。重要的是，这些影响强烈依赖于基线寻求刺激评分。总体而言，卡麦角林增加了对获胜概率信息的选择敏感性；同时，根据不同选项与潜在损失相关的幅度降低了区分能力。药物的最大影响在寻求刺激得分较低的参与者中观察到。这些发现提供了证据表明，人类的冒险行为可以通过多巴胺能药物直接操纵，但这种操纵的效果取决于基线寻求刺激特质的差异。这强调了在研究风险决策的操纵时考虑个体差异的重要性，并且可能与开发涉及人类过度冒险的疾病的药物治疗有关，例如病理性赌博。
