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

TY - JOUR

T1 - Serotonin transporter dosage modulates long-term decision-making in rat and human.

AU - Homberg, J.R.

AU - van den Bos, R.

AU - den Heijer, E.J.

AU - Suer, R.

AU - Cuppen, E.

N1 - Reporting year: 2008

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1016/j.neuropharm.2008.04.016

DO - 10.1016/j.neuropharm.2008.04.016

M3 - Article

SN - 0028-3908

VL - 55

SP - 80

EP - 84

JO - Neuropharmacology

JF - Neuropharmacology

IS - 1

ER -