Bidirectional interplay between methamphetamine and pulmonary infection: Impaired lung immunity and enhanced brain...

As a globally prevalent psychoactive stimulant, methamphetamine (METH) is linked to impaired immune function and higher susceptibility to infections like pneumonia. However, systematic studies on METH-related bacterial pneumonia-especially their bidirectional regulatory effects-remain scarce. This study established three mouse METH exposure models (acute, behavioral sensitization, chronic incremental) and induced pulmonary bacterial infection via Pseudomonas aeruginosa to observe METH's impact on post-infection survival. We also administered METH to mice with a pre-existing pulmonary infection induced by P. aeruginosa to test if pulmonary infection modulates METH's central effects. Results showed that, in all three models, METH administration reduced survival, worsened pulmonary histopathology, increased bacterial load, and suppressed pulmonary inflammatory responses in a time-dependent manner. In vitro experiments confirmed this: METH reduced phagocytic/digestive abilities of primary macrophages and murine alveolar macrophage (MH-S) cells. Notably, pre-existing pulmonary infection strongly modulated METH-induced brain changes: increasing apoptotic cell proportion, TNF-α expression, and activation of microglia/astrocytes. These findings first systematically demonstrate bidirectional interplay between METH exposure and pulmonary infection, reveal spatiotemporal dynamics in substance abuse-infection interactions, establish a theoretical framework for targeted interventions, and identify prior peripheral infection as an independent neuromodulation risk factor-offering a new paradigm for understanding substance abuse-related neuropathology.