Serotonin transporter dosage modulates long-term decision-making in rat and human

Neuropharmacology. 2008 Jul;55(1):80-4. doi: 10.1016/j.neuropharm.2008.04.016. Epub 2008 Apr 26.


Decision-making plays an important role in everyday life and is often disturbed in psychiatric conditions affected by the common human serotonin transporter promoter length polymorphism (5-HTTLPR). This raises the hypothesis that decision-making is modulated by the serotonergic system, but currently it is unclear how the 5-HTTLPR affects central serotonergic functioning. We tested healthy human volunteers genotyped for the 5-HTTLPR in the Iowa Gambling Task (IGT), which is one of the most frequently used neuropsychological tasks to assess decision-making. Furthermore, we tested female homozygous (SERT(-/-)) and heterozygous (SERT(+/-)) serotonin transporter knockout rats in a rodent version of the IGT. Women homozygous for the short (s) allele of the 5-HTTLPR were found to choose more disadvantageously than women homozygous for the long allele of the 5-HTTLPR as the IGT progressed. In the rat, SERT(-/-) and SERT(+/-) were associated with advantageous decision-making compared to SERT(+/+) as the IGT progressed. Combining the human and rat observations, we show that SERT dosage affects the maintenance of a once established choice option, irrespective of the choice (advantageous or disadvantageous) that has been made. We postulate that the SERT-mediated effects relate to deficits in the processing of choice outcome to guide subsequent choices in this gamble-based test, and that SERT(-/-) and SERT(+/-) rodent models in combination with studies in humans can be used to provide insight in the modulatory effects of 5-HTTLPR.

MeSH terms

  • Adult
  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal / physiology*
  • Decision Making / physiology*
  • Female
  • Gambling
  • Gene Dosage
  • Humans
  • Neuropsychological Tests
  • Rats
  • Risk-Taking*
  • Serotonin Plasma Membrane Transport Proteins / deficiency
  • Serotonin Plasma Membrane Transport Proteins / physiology*


  • Serotonin Plasma Membrane Transport Proteins