Physical exercise activates the μ-opioid system in human brain

Objectives Physical endurance exercise reduces stress and anxiety, elevates mood, and relieves pain, but the underlying neurobiological mechanisms responsible for these beneficial psychophysical effects remain largely unknown. The central opioidergic mechanisms likely modulate these effects. In this study, we sought to the opioid hypothesis of exercise-induced euphoria by measuring µ-opioid receptor availability in vivo in healthy males twice, before and after aerobic exercise.

Methods Five recreationally active healthy men (age: 24±2 years, BMI: 23±1.6, VO2max: 49.1±6.3 mL/kg/min) were studied with positron emission tomography (PET) and a bolus injection of [11C]carfentanil. Participants had two [11C]carfentanil PET scans in random order: after rest and after 60 min of aerobic endurance cycling, on separate days. Cycling was performed at a workload between aerobic and anaerobic thresholds (158±40 W) predetermined individually in maximal oxygen uptake test. Voxel-wise µ-opioid receptor availability was quantified with simplified reference tissue model using occipital cortex as the reference region, and compared between conditions using statistical parametric mapping.

Results Acute exercise increased the availability of µ-opioid receptors in anterior cingulate cortex, prefrontal and temporal cortex (cluster-level FDR-corrected p<0.05). A quantitative analysis based on regions of interest indicated that exercise increased µ-opioid receptor availability by about 10% in these brain regions.

Conclusions This study provides preliminary evidence that acute exercise modulates the brain µ-opioid system in recreationally active men. Activation of the brain µ-opioid may be responsible for various beneficial psychophysical effects of physical exercise. Individual differences in these mechanisms may reveal why some people enjoy physical exercise more than others, and may therefore have important public health implications.

Research Support Academy of Finland, Sigrid Juselius Foundation, Turku Collegium of Science and Medicine, Turku University Hospital