TY - JOUR
T1 - Dissociable Effects of Dopamine and Serotonin on Reversal Learning
AU - DenOuden, Hanneke E.M.
AU - Daw, Nathaniel D.
AU - Fernandez, Guillén
AU - Elshout, Joris A.
AU - Rijpkema, Mark
AU - Hoogman, Martine
AU - Franke, Barbara
AU - Cools, Roshan
N1 - Funding Information:
We thank Sabine Kooijman for logistic support; Angelien Heister, Remco Makkinje, and Marlies Naber for genotyping; and Bradley Doll, Sean Fallon, Michael Frank, Guillaume Sescousse, and Jennifer Cook for insightful discussions and feedback. This work makes use of the Brain Imaging Genetics (BIG) database, first established in Nijmegen, the Netherlands, in 2007. This resource is now part of Cognomics ( http://www.cognomics.nl ), a joint initiative by researchers of the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud University Medical Centre and the Max Planck Institute for Psycholinguistics in Nijmegen. The Cognomics Initiative is supported by the participating departments and centres and by external grants: the Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL), the Hersenstichting Nederland, and the Netherlands Organisation for Scientific Research. This study was also supported by a Research Vidi Grant to R.C. and a Research Veni Grant to H.d.O. from the Innovational Research Incentives Scheme of the Netherlands Organisation for Scientific Research as well as a Human Frontiers Science Program grant to Kae Nakamura, N.D., and R.C., and a James McDonnell scholar award to both R.C. and N.D. We wish to thank all who kindly participated in this research.
PY - 2013/11/20
Y1 - 2013/11/20
N2 - Serotonin and dopamine are speculated to subserve motivationally opponent functions, but this hypothesis has not been directly tested. We studied the role of these neurotransmitters in probabilistic reversal learning in nearly 700 individuals as a function of two polymorphisms in the genes encoding the serotonin and dopamine transporters (. SERT: 5HTTLPR plus rs25531; DAT1 3@UTR VNTR). A double dissociation was observed. The SERT polymorphism altered behavioral adaptation after losses, with increased lose-shift associated with L@ homozygosity, while leaving unaffected perseveration after reversal. In contrast, the DAT1 genotype affected the influence of prior choices on perseveration, while leaving lose-shifting unaltered. A model of reinforcement learning captured the dose-dependent effect of DAT1 genotype, such that an increasing number of 9R-alleles resulted in a stronger reliance on previous experience and therefore reluctance to update learned associations. These data provide direct evidence for doubly dissociable effects of serotonin and dopamine systems.
AB - Serotonin and dopamine are speculated to subserve motivationally opponent functions, but this hypothesis has not been directly tested. We studied the role of these neurotransmitters in probabilistic reversal learning in nearly 700 individuals as a function of two polymorphisms in the genes encoding the serotonin and dopamine transporters (. SERT: 5HTTLPR plus rs25531; DAT1 3@UTR VNTR). A double dissociation was observed. The SERT polymorphism altered behavioral adaptation after losses, with increased lose-shift associated with L@ homozygosity, while leaving unaffected perseveration after reversal. In contrast, the DAT1 genotype affected the influence of prior choices on perseveration, while leaving lose-shifting unaltered. A model of reinforcement learning captured the dose-dependent effect of DAT1 genotype, such that an increasing number of 9R-alleles resulted in a stronger reliance on previous experience and therefore reluctance to update learned associations. These data provide direct evidence for doubly dissociable effects of serotonin and dopamine systems.
UR - http://www.scopus.com/inward/record.url?scp=84888068462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888068462&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2013.08.030
DO - 10.1016/j.neuron.2013.08.030
M3 - Article
C2 - 24267657
AN - SCOPUS:84888068462
SN - 0896-6273
VL - 80
SP - 1090
EP - 1100
JO - Neuron
JF - Neuron
IS - 4
ER -