Neuroimmune signaling in alcohol use disorder

Pharmacol Biochem Behav. 2019 Feb:177:34-60. doi: 10.1016/j.pbb.2018.12.007. Epub 2018 Dec 24.


Alcohol use disorder (AUD) is a widespread disease with limited treatment options. Targeting the neuroimmune system is a new avenue for developing or repurposing effective pharmacotherapies. Alcohol modulates innate immune signaling in different cell types in the brain by altering gene expression and the molecular pathways that regulate neuroinflammation. Chronic alcohol abuse may cause an imbalance in neuroimmune function, resulting in prolonged perturbations in brain function. Likewise, manipulating the neuroimmune system may change alcohol-related behaviors. Psychiatric disorders that are comorbid with AUD, such as post-traumatic stress disorder, major depressive disorder, and other substance use disorders, may also have underlying neuroimmune mechanisms; current evidence suggests that convergent immune pathways may be involved in AUD and in these comorbid disorders. In this review, we provide an overview of major neuroimmune cell-types and pathways involved in mediating alcohol behaviors, discuss potential mechanisms of alcohol-induced neuroimmune activation, and present recent clinical evidence for candidate immune-related drugs to treat AUD.

Keywords: Addiction; Alcohol; Astrocyte; Comorbidity; Microglia; Neuroimmune.

Publication types

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

MeSH terms

  • Alcoholism / epidemiology*
  • Alcoholism / immunology*
  • Alcoholism / metabolism
  • Alcoholism / therapy
  • Animals
  • Brain / drug effects*
  • Brain / immunology
  • Brain / metabolism
  • Comorbidity
  • Depressive Disorder, Major / epidemiology*
  • Depressive Disorder, Major / immunology
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / therapy
  • Humans
  • Immunity, Innate / drug effects*
  • Immunomodulation
  • Mice
  • Neuroimmunomodulation*
  • Rats
  • Stress Disorders, Post-Traumatic / epidemiology*
  • Stress Disorders, Post-Traumatic / immunology
  • Stress Disorders, Post-Traumatic / metabolism
  • Stress Disorders, Post-Traumatic / therapy