The role of serotonin in reward, punishment and behavioural inhibition in humans: insights from studies with acute tryptophan depletion

Paul Faulkner, J F William Deakin

Research output: Contribution to journalReview articlepeer-review


Deakin and Graeff proposed that forebrain 5-hydroxytryptamine (5-HT) projections are activated by aversive events and mediate anticipatory coping responses including avoidance learning and suppression of the fight-flight escape/panic response. Other theories proposed 5-HT mediates aspects of behavioural inhibition or reward. Most of the evidence comes from rodent studies. We review 36 experimental studies in humans in which the technique of acute tryptophan depletion (ATD) was used to explicitly address the role of 5-HT in response inhibition, punishment and reward. ATD did not cause disinhibition of responding in the absence of rewards or punishments (9 studies). A major role for 5-HT in reward processing is unlikely but further tests are warranted by some ATD findings. Remarkably, ATD lessened the ability of punishments (losing points or notional money) to restrain behaviour without affecting reward processing in 7 studies. Two of these studies strongly indicate that ATD blocks 5-HT mediated aversively conditioned Pavlovian inhibition and this can explain a number of the behavioural effects of ATD.

Original languageEnglish
Pages (from-to)365-78
Number of pages14
JournalNeuroscience & Biobehavioral Reviews
Volume46 Pt 3
Early online date4 Sept 2014
Publication statusPublished - Oct 2014


  • Humans
  • Inhibition (Psychology)
  • PubMed
  • Punishment
  • Reward
  • Tryptophan
  • Journal Article
  • Review

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