TY - JOUR T1 - Low-Serotonin Levels Increase Delayed Reward Discounting in Humans JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4528 LP - 4532 DO - 10.1523/JNEUROSCI.4982-07.2008 VL - 28 IS - 17 AU - Nicolas Schweighofer AU - Mathieu Bertin AU - Kazuhiro Shishida AU - Yasumasa Okamoto AU - Saori C. Tanaka AU - Shigeto Yamawaki AU - Kenji Doya Y1 - 2008/04/23 UR - http://www.jneurosci.org/content/28/17/4528.abstract N2 - 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. ER -