Dissociable effects of dopamine and serotonin on reversal learning
Number of pages
SourceNeuron, 80, 4, (2013), pp. 1090-1100
Article / Letter to editor
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PI Group Motivational & Cognitive Control
PI Group MR Techniques in Brain Function
F.C. Donders Centre for Cognitive Neuroimaging
Subject150 000 MR Techniques in Brain Function; 170 000 Motivational & Cognitive Control; DCN MP - Plasticity and memory; DCN PAC - Perception action and control; DCN PAC - Perception action and control IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 3: Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory; ONCOL 3: Translational research NCMLS 2: Immune Regulation
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.
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