Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise

Front Neuroendocrinol. 2012 Aug;33(3):315-27. doi: 10.1016/j.yfrne.2012.09.003. Epub 2012 Sep 21.

Abstract

Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise.

Publication types

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

MeSH terms

  • Animals
  • Basal Ganglia / drug effects*
  • Basal Ganglia / physiology
  • Behavior, Animal / drug effects
  • Cytokines / physiology*
  • Dopamine / biosynthesis
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Fatigue / chemically induced
  • Glutamic Acid / metabolism
  • Humans
  • Illness Behavior / physiology
  • Inflammation / physiopathology*
  • Interferon-alpha / adverse effects
  • Macaca mulatta
  • Reward
  • Serotonin Uptake Inhibitors / therapeutic use
  • Synaptic Transmission / drug effects

Substances

  • Cytokines
  • Interferon-alpha
  • Serotonin Uptake Inhibitors
  • Glutamic Acid
  • Dopamine