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

NEUROPHARMACOLOGY

卷:55

Article

Homberg, Judith R.^1,2  van den Bos, Ruud^3,4  den Heijer, Esther^2,3  Suer, Remco³  Cuppen, Edwin² 

[1] Radboud Univ Nijmegen Med Ctr, Dept Cognit Neurosci, Donders Ctr Neurosci, NL-6525 GA Nijmegen, Netherlands

[2] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[3] Univ Utrecht, Fac Vet Med, Utrecht, Netherlands

[4] Univ Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

关键词: knockout rat;    5-HTTLPR;    Iowa Gambling Task;    prefrontal cortex;    serotonin transporter;    healthy volunteers;   

DOI  :  10.1016/j.neuropharm.2008.04.016

来源: Elsevier

【 摘 要 】

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. (c) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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