Amping up effort: effects of d-amphetamine on human effort-based decision-making.
Amping up effort: effects of d-amphetamine on human effort-based decision-making.
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DOI：
10.1523/jneurosci.4387-11.2011
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发表时间：
2011-11-16
期刊：
影响因子：
--
通讯作者：
de Wit H
中科院分区：
文献类型：
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作者：
Wardle MC;Treadway MT;Mayo LM;Zald DH;de Wit H
动物研究表明，神经递质多巴胺（DA）在决策中起着重要作用。在大鼠中，DA耗竭降低了对努力和概率成本的耐受性，而增强DA的药物增加了对这些成本的耐受性。然而，关于DA操纵对人类努力和概率成本的影响的数据仍然很少。目前的研究探讨了急性效应的d-安非他明，一种间接的DA受体激动剂，健康的人类志愿者的意愿，努力在不同水平的奖励价值和奖励概率的金钱奖励。根据临床前研究，我们预测安非他明会增加努力的程度，特别是当奖励概率较低时。在三个阶段中，17名健康的正常成年人在平衡双盲条件下接受安慰剂，d-苯丙胺10 mg和20 mg，并完成奖励任务的努力支出。与预测一致，安非他明增强了努力的意愿，特别是当奖励概率较低时。安非他明并没有改变奖励幅度的影响，愿意付出努力。安非他明加快任务的表现，但其心理影响并没有强烈的决策影响。这是第一次在人类中证明多巴胺能操纵改变了为获得奖励而付出努力的意愿。这些发现有助于阐明神经化学底物的选择，与多巴胺能功能障碍和动机缺陷为特征的神经精神疾病的影响。
Animal studies suggest the neurotransmitter dopamine (DA) plays an important role in decision-making. In rats, DA depletion decreases tolerance for effort and probability costs, while drugs enhancing DA increase tolerance for these costs. However, data regarding the effect of DA manipulations on effort and probability costs in humans remains scarce. The current study examined acute effects of d-amphetamine, an indirect DA agonist, on willingness of healthy human volunteers to exert effort for monetary rewards at varying levels of reward value and reward probability. Based on preclinical research, we predicted amphetamine would increase exertion of effort, particularly when reward probability was low. Over three sessions, 17 healthy normal adults received placebo, d-amphetamine 10 mg, and 20 mg under counterbalanced double-blind conditions and completed the Effort Expenditure for Rewards Task. Consistent with predictions, amphetamine enhanced willingness to exert effort, particularly when reward probability was lower. Amphetamine did not alter effects of reward magnitude on willingness to exert effort. Amphetamine sped task performance, but its psychomotor effects were not strongly related to its effects on decision-making. This is the first demonstration in humans that dopaminergic manipulations alter willingness to exert effort for rewards. These findings help elucidate neurochemical substrates of choice, with implications for neuropsychiatric diseases characterized by dopaminergic dysfunction and motivational deficits.