1. ¹Department of Experimental Psychology, University of Cambridge, Cambridge, UK
2. ²Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
3. ³MRC Cognition and Brain Sciences Unit, Cambridge, UK
4. ⁴Department of Psychology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA
5. ⁵Institute of Brain and Behavior, University of Maastricht, Maastricht, The Netherlands

Correspondence: Dr R Cools, Helen Wills Neuroscience Institute, 132 Barker Hall, Berkeley, CA 94720-3190, USA. Tel: +1 510 642 2839; Fax: +1 510 642 3192; E-mail: roshanco@berkeley.edu

Received 11 May 2004; Revised 27 October 2004; Accepted 29 December 2004; Published online 16 March 2005.

Abstract

Serotonin (5-HT) is well known to affect the motivational properties of stimuli predictive of rewards as well as the inhibitory control of behavior. Here, central 5-HT depletion was induced by the acute tryptophan (TRP) depletion (ATD) procedure in young healthy volunteers to examine the role of 5-HT in motivated action and prepotent response inhibition. A novel reaction-time task, tailored to individual differences in general cognitive speed, was employed to measure the guidance of behavior by motivationally relevant signals predictive of reinforcement likelihood, while the stop-signal reaction-time task was used to measure response inhibition. Following the TRP-balancing control drink, cues predictive of high-reinforcement certainty induced faster, but less accurate responses compared with cues predictive of lower reinforcement certainty. Depletion of central 5-HT modulated this coupling between motivation and action by slowing responses and increasing accuracy as a function of incentive certainty. These effects of ATD on motivated action correlated highly with individual differences in the personality trait of Nonplanning Impulsiveness (Barratt Impulsivity Scale (BIS-11)), so that strongest effects on motivated action were observed in high-impulsive individuals. By contrast, ATD left unaltered the ability to inhibit prepotent responses. Our findings may have implications for a variety of neuropsychiatric disorders including impulsive aggressive disorders and depression.