Beyond negative valence: 2-week administration of a serotonergic antidepressant enhances both reward and effort learning signals

PLoS Biol. 2017 Feb 16;15(2):e2000756. doi: 10.1371/journal.pbio.2000756. eCollection 2017 Feb.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / pharmacology*
  • Citalopram / administration & dosage*
  • Citalopram / pharmacology
  • Humans
  • Learning / drug effects*
  • Magnetic Resonance Imaging
  • Reward*
  • Selective Serotonin Reuptake Inhibitors / administration & dosage*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin / metabolism
  • Task Performance and Analysis*

Substances

  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin