Aerobic Fitness Is Associated with Cerebral μ-Opioid Receptor Activation in Healthy Humans

Introduction Central μ-opioid receptors (MORs) modulate affective responses to physical exercise. Individuals with higher aerobic fitness report greater exercise-induced mood improvements than those with lower fitness, but the link between cardiorespiratory fitness and the MOR system remains unresolved. Here we tested whether maximal oxygen uptake (VO2peak) and physical activity level are associated with cerebral MOR availability and whether these phenotypes predict endogenous opioid release after a session of exercise. Methods We studied 64 healthy lean men who performed a maximal incremental cycling test for VO2peak determination, completed a questionnaire assessing moderate-to-vigorous physical activity (MVPA; in minutes per week), and underwent positron emission tomography with [11C]carfentanil, a specific radioligand for MOR. A subset of 24 subjects underwent additional positron emission tomography scan also after a 1-h session of moderate-intensity exercise and 12 of them also after a bout of high-intensity interval training. Results Higher self-reported MVPA level predicted greater opioid release after high-intensity interval training, and both VO2peak and MVPA level were associated with a larger decrease in cerebral MOR binding after aerobic exercise in the ventral striatum, orbitofrontal cortex, and insula. That is, more trained individuals showed greater opioid release acutely after exercise in brain regions especially relevant for reward and cognitive processing. Fitness was not associated with MOR availability. Conclusions We conclude that regular exercise training and higher aerobic fitness may induce neuroadaptation within the MOR system, which might contribute to improved emotional and behavioral responses associated with long-term exercise.