[Research advances in the mechanisms of neuroinflammatory in substance addiction]

Neuroinflammation is an important pathological mechanism underlying the development and progression of substance addiction, as well as relapse following withdrawal. Repeated exposure to addictive substances can activate microglia and astrocytes through multiple pathways, including neuronal injury, oxidative stress, pattern-recognition receptors, and inflammasomes, thereby disrupting glutamate homeostasis, aberrantly altering synaptic pruning, and modifying synaptic plasticity. These changes, in turn, affect neural circuits involved in reward, stress, and executive function. Concurrently, increased blood-brain barrier permeability, dysregulated meningeal immune responses, impaired glymphatic clearance, and disruption of the brain-gut axis can promote aberrant crosstalk between central and peripheral immune signals and sustain inflammatory states. Although psychostimulants, opioids, and alcohol initiate neuroinflammation through distinct mechanisms, they ultimately converge on glial reactivity, disruption of synaptic homeostasis, and alterations in addiction-related behaviors. Here, we discuss the mechanisms underlying neuroinflammation in substance addiction, summarize recent advances in immune-targeted interventions, and highlight the challenges associated with their clinical translation.