Low-Serotonin Levels Increase Delayed Reward Discounting in Humans
Low-Serotonin Levels Increase Delayed Reward Discounting in Humans
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DOI：
10.1523/jneurosci.4982-07.2008
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发表时间：
2008-04
期刊：
影响因子：
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通讯作者：
N. Schweighofer;M. Bertin;K. Shishida;Y. Okamoto;Saori C. Tanaka;S. Yamawaki;K. Doya
中科院分区：
文献类型：
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作者：
N. Schweighofer;M. Bertin;K. Shishida;Y. Okamoto;Saori C. Tanaka;S. Yamawaki;K. Doya
先前的动物实验已经表明，血清素参与了冲动选择的控制，其特征是对较小的即时奖励的偏好高于较大的延迟奖励。然而，先前在5-羟色胺操纵下进行的人类研究要么对冲动性的影响没有定论，要么对行动奖励学习的速度或行动选择的最优性有影响。在这里，我们操纵健康志愿者的饮食色氨酸消耗和负荷的中枢多巴胺能水平。受试者进行了一个“动态”的延迟奖励选择任务，需要不断更新的奖励价值估计，以最大限度地提高总收益。通过使用延迟奖励选择学习的计算模型，我们估计了在低、正常和高血清素条件下控制受试者奖励选择的参数。我们发现，与控制组和高血清素组相比，低血清素组的小奖励选择比例增加，延迟奖励折扣率增加。有没有显着差异的条件之间的学习速度的估计延迟奖励值或奖励选择的变化。因此，与之前的动物实验一致，我们的研究结果表明，低血清素水平会使人类延迟奖励折扣变陡。我们以前和现在的研究结果表明，血清素可能通过调节平行皮质基底神经节回路中的特定回路来调节延迟奖励折扣率。
Previous animal experiments have shown that serotonin is involved in the control of impulsive choice, as characterized by high preference for small immediate rewards over larger delayed rewards. Previous human studies under serotonin manipulation, however, have been either inconclusive on the effect on impulsivity or have shown an effect in the speed of action–reward learning or the optimality of action choice. Here, we manipulated central serotonergic levels of healthy volunteers by dietary tryptophan depletion and loading. Subjects performed a “dynamic” delayed reward choice task that required a continuous update of the reward value estimates to maximize total gain. By using a computational model of delayed reward choice learning, we estimated the parameters governing the subjects' reward choices in low-, normal, and high-serotonin conditions. We found an increase of proportion in small reward choices, together with an increase in the rate of discounting of delayed rewards in the low-serotonin condition compared with the control and high-serotonin conditions. There were no significant differences between conditions in the speed of learning of the estimated delayed reward values or in the variability of reward choice. Therefore, in line with previous animal experiments, our results show that low-serotonin levels steepen delayed reward discounting in humans. The combined results of our previous and current studies suggest that serotonin may adjust the rate of delayed reward discounting via the modulation of specific loops in parallel corticobasal ganglia circuits.