title: Beyond negative valence: 2-week administration of a serotonergic antidepressant enhances both reward and effort learning signals.
abstract: To make good decisions, humans need to learn about and integrate different sources of appetitive and aversive information. While serotonin has been linked to value-based decision-making, its role in learning is less clear, with acute manipulations often producing inconsistent results. Here, we show that when the effects of a selective serotonin reuptake inhibitor (SSRI, citalopram) are studied over longer timescales, learning is robustly improved. We measured brain activity with functional magnetic resonance imaging (fMRI) in volunteers as they performed a concurrent appetitive (money) and aversive (effort) learning task. We found that 2 weeks of citalopram enhanced reward and effort learning signals in a widespread network of brain regions, including ventromedial prefrontal and anterior cingulate cortex. At a behavioral level, this was accompanied by more robust reward learning. This suggests that serotonin can modulate the ability to learn via a mechanism that is independent of stimulus valence. Such effects may partly underlie SSRIs' impact in treating psychological illnesses. Our results highlight both a specific function in learning for serotonin and the importance of studying its role across longer timescales.
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.|Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
authors.forename: Jacqueline
authors.identifier: 0000-0001-9969-1355
authors.initials: J
authors.lastname: Scholl
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
authors.forename: Nils
authors.initials: N
authors.lastname: Kolling
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.|Department of Psychiatry, University of Oxford, Oxford, United Kingdom.|Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Nelissen
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Browning
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.|Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Matthew F S
authors.initials: MF
authors.lastname: Rushworth
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D015283:Citalopram / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007858:Learning / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D012201:Reward; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D013647:Task Performance and Analysis
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors