Exercise-induced neuropeptidergic and neurochemical neuroadaptation in stress regulation and emotional disorders.

Exercise is increasingly recognized not only as a behavioral and preventive health intervention but also as a biologically active stimulus that may influence stress-responsive neural systems across molecular, autonomic, neurochemical, neuroimmune, and network levels. Evidence from human intervention studies, neuroimaging research, peripheral biomarker analyses, and preclinical models suggests that repeated physical activity may modulate pathways involved in emotional regulation, motivational processing, stress responsivity, interoceptive signaling, and adaptive neuroplasticity. However, the strength of evidence varies across mechanisms, and several cellular, receptor-level, and circuit-specific processes remain supported primarily by animal studies or indirect peripheral markers rather than direct causal demonstration in humans. This review synthesizes experimental, clinical, and conceptual evidence on exercise-induced neuroadaptation, with emphasis on neurochemical and neuropeptidergic mechanisms relevant to stress regulation and emotional disorders. We discuss exercise-associated adaptations involving dopaminergic, serotonergic, noradrenergic, glutamatergic, GABAergic, endocannabinoid, and opioid-related signaling, together with stress-responsive neuropeptides including corticotropin-releasing hormone, neuropeptide Y, oxytocin, orexin, β-endorphin, and substance P. Beyond isolated transmitter systems, we highlight interactions among hypothalamic peptidergic regulation, autonomic function, neurotrophic signaling, neuroimmune pathways, and large-scale neural network organization. We also introduce the biphasic neuroadaptation of the exercise framework, the neuroadaptive feedback loop of movement, and personalized neuromodulatory exercise profiling as heuristic models for organizing existing evidence rather than established clinical paradigms. Collectively, exercise may represent an emerging biologically informed neuromodulatory approach, although precision-based clinical application requires stronger causal human evidence, standardized biomarkers, and longitudinal validation.