Can't or Won't? Immunometabolic Constraints on Dopaminergic Drive

Trends Cogn Sci. 2019 May;23(5):435-448. doi: 10.1016/j.tics.2019.03.003. Epub 2019 Apr 2.


Inflammatory cytokines have been shown to have a direct effect on mesolimbic dopamine (DA) that is associated with a reduced willingness to expend effort for reward. To date, however, the broader implications of this communication between inflammation and mesolimbic DA have yet to be explored. Here, we suggest that the metabolic demands of chronic low-grade inflammation induce a reduction of striatal DA that in turn leads to a steeper effort-discounting curve because of reduced perceived ability (can't) versus preference (won't) for reward. This theoretical framework can inform how the mesolimbic DA system responds to increased immunometabolic demands during chronic inflammation, ultimately contributing to motivational impairments in psychiatric and other medical disorders.

Keywords: cytokines; dopamine; effort; immunometabolism; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Dopaminergic Neurons / immunology
  • Dopaminergic Neurons / physiology*
  • Energy Metabolism / immunology
  • Energy Metabolism / physiology
  • Humans
  • Inflammation / immunology
  • Inflammation / physiopathology*
  • Limbic System / immunology
  • Limbic System / physiology