Tryptophan depletion promotes habitual over goal-directed control of appetitive responding in humans

Background: Optimal behavioural performance results from a balance between goal-directed and habitual systems of behavioural control, which are modulated by ascending monoaminergic projections. While the role of the dopaminergic system in behavioral control has been recently addressed, the extent to which changes in global serotonin (5-HT) neurotransmission could influence these two systems is still poorly understood.

Methods: We employed the dietary acute tryptophan depletion procedure (ATD) to reduce 5-HT neurotransmission in 18 healthy volunteers and 18 matched controls. We used a 3-stage instrumental learning paradigm that includes an initial instrumental learning stage, a subsequent outcome-devaluation test, and a slip-of-action stage, which directly tests the balance between hypothetical goal-directed and habitual systems. We also employed a separate response inhibition control test to assess the behavioural specificity of the results.

Results: ATD produced a shift of behavioural performance towards habitual responding as indexed by performance on the slip-of-action test. Moreover, greater habitual responding in the ATD group was predicted by a steeper decline in plasma tryptophan levels. In contrast, ATD left intact the ability to use discriminative stimuli to guide instrumental choice as indexed by the instrumental learning stage and did not impair inhibitory response control.

Conclusions: The major implication of this study is that 5-HT modulates the balance between goal-directed and S-R habitual systems of behavioural control. Our findings thus imply that diminished 5-HT neurotransmission shifts behavioural control towards habitual responding.