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The Journal of Neuroscience, April 23, 2008, 28(17):4528-4532; doi:10.1523/JNEUROSCI.4982-07.2008

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Brief Communications
Low-Serotonin Levels Increase Delayed Reward Discounting in Humans

Nicolas Schweighofer,¹ Mathieu Bertin,^2,5 Kazuhiro Shishida,³ Yasumasa Okamoto,³ Saori C. Tanaka,² Shigeto Yamawaki,³ and Kenji Doya^2,4

¹Department of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California 90089, ²Computational Neuroscience Laboratories, Advanced Telecommunications Research Institute International, Kyoto 619-0288, Japan, ³Department of Psychiatry and Neurosciences, Hiroshima University, Higashihiroshima 739-8526, Japan, ⁴Okinawa Institute of Science and Technology, Okinawa 904-0411, Japan, and ⁵Laboratoire d'Informatique de Paris 6, Université Paris 6 Pierre et Marie Curie, 75005 Paris, France

Correspondence should be addressed to Nicolas Schweighofer, Department of Biokinesiology and Physical Therapy, University of Southern California, 1450 East Alcazar Street, Los Angeles, CA 90089. Email: schweigh{at}usc.edu

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.

Key words: serotonin; delay reward discounting; reinforcement learning model; tryptophan; decision; learning

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Received Nov. 7, 2007; revised March 19, 2008; accepted March 19, 2008.

Correspondence should be addressed to Nicolas Schweighofer, Department of Biokinesiology and Physical Therapy, University of Southern California, 1450 East Alcazar Street, Los Angeles, CA 90089. Email: schweigh{at}usc.edu

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