Neuroimmune signaling in alcohol use disorder

• Published in: Pharmacology, biochemistry and behavior Vol. 177; pp. 34 - 60
• Main Authors: Erickson, Emma K., Grantham, Emily K., Warden, Anna S., Harris, R.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2019
• Subjects: Addiction; Alcohol; Alcoholism - epidemiology; Alcoholism - immunology; Alcoholism - metabolism; Alcoholism - therapy; Animals; Astrocyte; 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; Microglia; Neuroimmune; Neuroimmunomodulation; Rats; Stress Disorders, Post-Traumatic - epidemiology; Stress Disorders, Post-Traumatic - immunology; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - therapy; Alcohol; Astrocyte; Addiction; Comorbidity; Neuroimmune; Microglia
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2018.12.007

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.
•Alcohol exposure perturbs innate immune signaling in brain.•A wide array of neuroimmune molecules regulate behavioral responses to alcohol.•Microglia and astrocyte dysfunction may contribute to addictive behaviors.•Neuroimmune imbalance may confer vulnerability to psychiatric disorders.•Immunomodulatory drugs are new candidates for treating alcohol use disorder.