Aerobic fitness is associated with cerebral mu-opioid receptor availability and activation in healthy humans

Central mu-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 following aerobic exercise. 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, min/week), and underwent positron emission tomography with [11C]carfentanil, a specific radioligand for MOR. A subset of 24 subjects underwent additional PET scan also after a one-hour session of moderate-intensity exercise. Higher VO2peak and self-reported MVPA level were associated with larger decrease in cerebral MOR binding after aerobic exercise in ventral striatum, orbitofrontal cortex and insula. That is, higher fit and more trained individuals showed greater opioid release acutely following exercise in brain regions especially relevant for reward and cognitive processing. Higher VO2peak also associated with lower baseline BPND in the reward and pain circuits, i.e., in frontal and cingulate cortices as well as in temporal lobes and subcortically in thalamus and putamen. We conclude that higher aerobic fitness and regular exercise training may induce neuroadaptation within the MOR system which might contribute to improved emotional and behavioural responses associated with long-term exercise.