Affective and decision functions of serotonin Roshan Cools Radboud University Medical Center, Department of Psychiatry Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour The ascending monoamine neuromodulatory systems are implicated in a wide variety of healthy and disordered functions. In the case of dopamine notable progress has been made in the last decade or two. In particular, models of reinforcement learning have been used as a framework to interpret and connect observations that dopamine is involved, on the one hand, in reward and motivation, and on the other in behavioral activation or the vigor of movement. By contrast, although the neuromodulator serotonin has functional and clinical importance at least equal to that of dopamine (e.g., it is implicated in impulsivity, depression, and pain), there is no similarly well-developed framework for understanding any of its roles. In this talk I will present data from a series of experiments with human volunteers, in which effects of central serotonin levels were studied by means of the dietary acute tryptophan depletion procedure and genetic approaches. Data demonstrate that such manipulation of serotonin has effects along two similar axes: a motivational (aversive processing) as well as an activational axis (inhibiting behavioral responses). We put forward the hypothesis that effects of serotonin can best be understood as serving to couple these two axes rather than affecting them independently.