The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications

Curr Top Behav Neurosci. 2017;31:199-219. doi: 10.1007/7854_2016_13.

Abstract

Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the basal ganglia and dopamine to mediate depressive symptoms related to motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal responses to hedonic reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine, all of which correlate with symptoms of anhedonia, fatigue, and psychomotor retardation. Similar relationships between alterations in dopamine-relevant corticostriatal reward circuitry and symptoms of anhedonia and psychomotor slowing have also been observed in patients with major depression who exhibit increased peripheral cytokines and other inflammatory markers, such as C-reactive protein. Of note, these inflammation-associated depressive symptoms are often difficult to treat in patients with medical illnesses or major depression. Furthermore, a wealth of literature suggests that inflammation can decrease dopamine synthesis, packaging, and release, thus sabotaging or circumventing the efficacy of standard antidepressant treatments. Herein, the mechanisms by which inflammation and cytokines affect dopamine neurotransmission are discussed, which may provide novel insights into treatment of inflammation-related behavioral symptoms that contribute to an inflammatory malaise.

Keywords: Anhedonia; Cytokines; Depression; Dopamine; In vivo microdialysis; Inflammation; Motivation; Motor slowing; Neuroimaging; Striatum.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism*
  • Depressive Disorder / drug therapy
  • Depressive Disorder / etiology
  • Depressive Disorder / metabolism*
  • Dopamine / metabolism*
  • Humans
  • Inflammation / complications
  • Inflammation / metabolism*

Substances

  • Cytokines
  • Dopamine