Dissociable Effects of Dopamine and Serotonin on Reversal Learning

Hanneke E.M. DenOuden, Nathaniel D. Daw, Guillén Fernandez, Joris A. Elshout, Mark Rijpkema, Martine Hoogman, Barbara Franke, Roshan Cools

Research output: Contribution to journalArticlepeer-review

170 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1090-1100
Number of pages11
Issue number4
StatePublished - Nov 20 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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