title: Dissociable effects of dopamine and serotonin on reversal learning.
abstract: 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.
authors.affiliation: Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen 6500, the Netherlands; Department of Psychology, New York University, New York, NY 10003, USA. Electronic address: h.denouden@gmail.com.
authors.forename: Hanneke E M
authors.initials: HE
authors.lastname: den Ouden
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Daw
authors.forename: Guillén
authors.initials: G
authors.lastname: Fernandez
authors.forename: Joris A
authors.initials: JA
authors.lastname: Elshout
authors.forename: Mark
authors.initials: M
authors.lastname: Rijpkema
authors.forename: Martine
authors.initials: M
authors.lastname: Hoogman
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Roshan
authors.initials: R
authors.lastname: Cools
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology; D000328:Adult; D000465:Algorithms; D000483:Alleles; D003198:Computer Simulation; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D005715:Gambling / Q000523:psychology; D005838:Genotype; D006801:Humans; D008297:Male; D008959:Models, Neurological; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D012054:Reinforcement, Psychology; D012193:Reversal Learning / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004247:DNA; D004298:Dopamine