Serotonin depletion induces 'waiting impulsivity' on the human four-choice serial reaction time task: cross-species translational significance

Abstract

Convergent results from animal and human studies suggest that reducing serotonin neurotransmission promotes impulsive behavior. Here, serotonin depletion was induced by the dietary tryptophan depletion procedure (TD) in healthy volunteers to examine the role of serotonin in impulsive action and impulsive choice. We used a novel translational analog of a rodent 5-choice serial reaction time task (5-CSRTT)-- the human 4-CSRTT--and a reward delay-discounting questionnaire to measure effects on these different forms of 'waiting impulsivity'. There was no effect of TD on impulsive choice as indexed by the reward delay-discounting questionnaire. However, TD significantly increased 4-CSRTT premature responses (or impulsive action), which is remarkably similar to the previous findings of effect of serotonin depletion on rodent 5-CSRTT performance. Moreover, the increased premature responding in TD correlated significantly with individual differences on the motor impulsivity subscale of the Barratt Impulsivity Scale. TD also improved the accuracy of performance and speeded responding, possibly indicating enhanced attention and reward processing. The results suggest: (i) the 4-CSRTT will be a valuable addition to the tests already available to measure impulsivity in humans in a direct translational analog of a test extensively used in rodents; (ii) TD in humans produces a qualitatively similar profile of effects to those in rodents (ie, enhancing premature responding), hence supporting the conclusion that TD in humans exerts at least some of its effects on central serotonin; and (iii) this manipulation of serotonin produces dissociable effects on different measures of impulsivity, suggesting considerable specificity in its modulatory role.

Figures

Figure 1

Four-choice serial reaction time task (4-CSRTT): Participants were instructed to press and hold down the space bar. The press of the space bar indicated ‘cue onset' and four empty boxes appeared on the screen. The participants were instructed to release the space bar and touch the box in which the target (green circle) had appeared. They were asked to respond as quickly as possible. Premature release of the space bar prior to onset of the target (premature responses) was a primary outcome measure of the task.

Figure 2

Significant main outcome measures of the 4-CSRTT: premature responses, accuracy, and motivational index. Reported as Mean±SEM values. *P<0.05; Con, control group; TD, tryptophan depleted group.