Serotonin transporter dosage modulates long-term decision-making in rat and human.
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.
Department of Cognitive Neuroscience, Donders Centre for Neuroscience, UMC St. Radboud, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands. j.homberg@cns.umcn.nl
Judith R
JR
Homberg
Ruud
R
van den Bos
Esther
E
den Heijer
Remco
R
Suer
Edwin
E
Cuppen
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology*; D003657:Decision Making / Q000502:physiology*; D005260:Female; D005715:Gambling; D018628:Gene Dosage; D006801:Humans; D009483:Neuropsychological Tests; D051381:Rats; D012309:Risk-Taking; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency / Q000502:physiology*
D050486:Serotonin Plasma Membrane Transport Proteins