Pharmacological evidence for the implication of noradrenaline in effort

PLoS Biol. 2020 Oct 12;18(10):e3000793. doi: 10.1371/journal.pbio.3000793. eCollection 2020 Oct.

Abstract

The trade-off between effort and reward is one of the main determinants of behavior, and its alteration is at the heart of major disorders such as depression or Parkinson's disease. Monoaminergic neuromodulators are thought to play a key role in this trade-off, but their relative contribution remains unclear. Rhesus monkeys (Macaca mulatta) performed a choice task requiring a trade-off between the volume of fluid reward and the amount of force to be exerted on a grip. In line with a causal role of noradrenaline in effort, decreasing noradrenaline levels with systemic clonidine injections (0.01 mg/kg) decreased exerted force and enhanced the weight of upcoming force on choices, without any effect on reward sensitivity. Using computational modeling, we showed that a single variable ("effort") could capture the amount of resources necessary for action and control both choices (as a variable for decision) and force production (as a driving force). Critically, the multiple effects of noradrenaline manipulation on behavior could be captured by a specific modulation of this single variable. Thus, our data strongly support noradrenaline's implication in effort processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Choice Behavior / drug effects
  • Clonidine / pharmacology
  • Female
  • Macaca mulatta
  • Male
  • Models, Biological
  • Norepinephrine / pharmacology*
  • Placebos
  • Reward
  • Task Performance and Analysis

Substances

  • Placebos
  • Clonidine
  • Norepinephrine

Grants and funding

Fondation de France (recherche en psychiatrie) to SB. Recurrent founding from CNRS and ICM to SB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.