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- Article] Serotonin transporter dosage modulates long-term decision-making in rat and human
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DocNo of ILP: 3750
Doc. Type: Article
Title: Serotonin transporter dosage modulates long-term decision-making in rat and human
Authors: Homberg, JR; van den Bos, R; den Heijer, E; Suer, R; Cuppen, E
Full Name of Authors: Homberg, Judith R.; van den Bos, Ruud; den Heijer, Esther; Suer, Remco; Cuppen, Edwin
Keywords by Author: knockout rat; 5-HTTLPR; Iowa Gambling Task; prefrontal cortex; serotonin transporter; healthy volunteers
Keywords Plus: IOWA GAMBLING TASK; PREFRONTAL CORTEX; SEX-DIFFERENCES; AMYGDALA; POLYMORPHISM; DAMAGE; GENE; FLEXIBILITY; AMBIGUITY; ANXIETY
Abstract: 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.
Cate of OECD: Basic medicine
Year of Publication: 2008
Business Area: gamble
Detail Business: gamble
Country: England
Study Area: female, decision
Name of Journal: NEUROPHARMACOLOGY
Language: English
Country of Authors: [Homberg, Judith R.] Radboud Univ Nijmegen Med Ctr, Dept Cognit Neurosci, Donders Ctr Neurosci, NL-6525 GA Nijmegen, Netherlands; [Homberg, Judith R.; den Heijer, Esther; Cuppen, Edwin] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands; [van den Bos, Ruud; den Heijer, Esther; Suer, Remco] Univ Utrecht, Fac Vet Med, Utrecht, Netherlands; [van den Bos, Ruud] Univ Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands
Press Adress: Homberg, JR (reprint author), Radboud Univ Nijmegen Med Ctr, Dept Cognit Neurosci, Donders Ctr Neurosci, Geert Grootepl 28, NL-6525 GA Nijmegen, Netherlands.
Email Address: j.homberg@cns.umcn.nl
Citaion: Cuppen, Edwin/0000-0002-0400-9542
Funding:
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Number of Citaion: 36
Publication: PERGAMON-ELSEVIER SCIENCE LTD
City of Publication: OXFORD
Address of Publication: THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
ISSN: 0028-3908
29-Character Source Abbreviation: NEUROPHARMACOLOGY
ISO Source Abbreviation: Neuropharmacology
Volume: 55
Version: 1
Start of File: 80
End of File: 84
DOI: 10.1016/j.neuropharm.2008.04.016
Number of Pages: 5
Web of Science Category: Neurosciences; Pharmacology & Pharmacy
Subject Category: Neurosciences & Neurology; Pharmacology & Pharmacy
Document Delivery Number: 332AT
Unique Article Identifier: WOS:000258054700011
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