[Research advances in neuroinflammatory mechanisms of substance addiction]

Substance addiction is a chronic psychiatric disorder characterized by compulsive substance use, impaired behavioral control, and high relapse rates. Although mesolimbic dopaminergic reward system dysfunction is a key neurobiological substrate of substance addiction, it cannot fully explain persistent drug craving, addiction-related memory, or compulsive drug-seeking and drug-taking behaviors after abstinence. Repeated exposure to addictive substances can induce oxidative stress, activation of pattern-recognition receptors, increased blood-brain barrier permeability, and gut-brain axis dysregulation. These changes induce reactive microglial and astrocytic phenotypes and disrupt central-peripheral immune crosstalk. Persistent neuroinflammation induced by addictive substance exposure may alter glutamate homeostasis, complement-mediated synaptic pruning, extracellular matrix remodeling, and plasticity in reward, stress, and executive-control circuits. These alterations are thought to contribute to addiction-related memory consolidation, increased relapse risk, and comorbid psychiatric and behavioral abnormalities. This review summarizes neuroimmune regulation in the brain, central-peripheral immune interactions, and substance-specific neuroinflammatory mechanisms. It also discusses recent advances and challenges in immune-targeted pharmacological and non-pharmacological interventions.