Kambeitz Joseph, la Fougère Christian, Werner Natalie, Pogarell Oliver, Riedel Michael, Falkai Peter, Ettinger Ulrich
Department of Psychiatry, Ludwig-Maximilian-University Munich, Munich, Germany.
Department of Nuclear Medicine, University of Tübingen, Tübingen, Germany.
Eur Neuropsychopharmacol. 2016 Jun;26(6):938-47. doi: 10.1016/j.euroneuro.2016.03.011. Epub 2016 Apr 22.
Our everyday-life comprises a multitude of decisions that we take whilst trying to maximize advantageous outcomes, limit risks and update current needs. The cognitive processes that guide decision making as well as the brain circuits they are based on are only poorly understood. Numerous studies point to a potential role of dopamine and nicotine in decision making but less is known about their interactions. Here, 26 healthy male subjects performed the Iowa Gambling Task (IGT) in two sessions following the administration of either nicotine or placebo. Striatal dopamine transporter (DAT) binding was measured by single-photon emission computed tomography (SPECT). Results indicate that lower DAT levels were associated with better performance in the IGT (p=0.0004). Cognitive modelling analysis using the prospect valence learning (PVL) model indicated that low DAT subjects' performance deteriorated following nicotine administration as indicated by an increased learning rate and a decreased response consistency. Our results shed light on the neurochemistry underlying reward-based decision making in humans by demonstrating a significant interaction between nicotine and the DAT. The observed interaction is consistent with the hypothesized associations between DAT expression and extracellular dopamine levels, suggestive of an inverted U-shape relationship between baseline dopamine and magnitude in response to a pro-dopaminergic compound. Our findings are of particular interest in the context of psychiatric disorders where aberrant decision making represents a part of the core symptomatology, such as addiction, schizophrenia or depression.
我们的日常生活包含众多决策，我们在做这些决策时试图最大化有利结果、限制风险并更新当前需求。然而，指导决策的认知过程及其所基于的脑回路却鲜为人知。众多研究指出多巴胺和尼古丁在决策中可能发挥作用，但它们之间的相互作用却知之甚少。在此，26名健康男性受试者在接受尼古丁或安慰剂后分两个阶段进行了爱荷华赌博任务（IGT）。通过单光子发射计算机断层扫描（SPECT）测量纹状体多巴胺转运体（DAT）结合情况。结果表明，较低的DAT水平与IGT中更好的表现相关（p = 0.0004）。使用前景效价学习（PVL）模型的认知建模分析表明，低DAT受试者在服用尼古丁后表现变差，表现为学习率增加和反应一致性降低。我们的研究结果通过证明尼古丁与DAT之间的显著相互作用，揭示了人类基于奖励的决策背后的神经化学机制。观察到的相互作用与DAT表达和细胞外多巴胺水平之间的假设关联一致，提示基线多巴胺与对促多巴胺能化合物反应强度之间呈倒U形关系。我们的研究结果在精神疾病背景下尤其令人关注，在这些疾病中，异常决策是核心症状的一部分，如成瘾、精神分裂症或抑郁症。
