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

Abstract

IntroductionCentral 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 (V̇O2peak) and physical activity level are associated with cerebral MOR availability and whether these phenotypes predict endogenous opioid release after a session of exercise.MethodsWe studied 64 healthy lean men who performed a maximal incremental cycling test for V̇O2peak 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.ResultsHigher self-reported MVPA level predicted greater opioid release after high-intensity interval training, and both V̇O2peak 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.ConclusionsWe 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.

Bodily maps of exercise-induced sensations

“…Given the well-established regulatory role of exercise intensity on affective responses of exercise [8,38], it is not surprising that exercise intensity modulates also the overall bodily experience of exhaustion. Moreover, we found that higher self-assessed fitness level was associated with greater reductions of bodily sensations of pain and discomfort after exercise, which may be linked with greater exercise-induced endogenous opioid release observed in individuals with higher cardiorespiratory fitness and physical activity level [50]. Although these are just simple one-dimensional indicators, they however suggest that the self-reported bodily sensations have physiological basis [30], as previously shown for RPE [35,51].…”

Decreased Exercise-Induced Changes in Prefrontal Cortex Hemodynamics Are Associated With Depressive Symptoms

“…For example, collapsing across different executive function tasks might result in BA10 activation that explains little variability in depression, as was the case in the present study, but that the exercise effect in this PFC subregion was sensitive to how aerobically fit people were might suggest an important role of fitness in treating depression. That is, it is plausible that physical fitness works to correct issues of abnormal activity in rostral PFC (e.g., Saanijoki et al, 2022 ). Future investigations might further elucidate this possibility, but the present findings represent a starting point for highlighting the potential interrelations between the PFC, physical activity, and depressive symptoms, as well as between physical activity, rostral PFC, and aerobic fitness.…”

A Molecular Toolbox of Positron Emission Tomography Tracers for General Anesthesia Mechanism Research

“…78 With an optimized 11 C-labeling method using ethanol as the solvent and a C2 solid-phase extraction cartridge for quick purification, the preparation of [ 11 C]22 achieved RCY = 4 ± 1%, RCP = 97 ± 2%, and A m = 693 ± 447 GBq/μmol. 72 Although the strong potency of CFN as a highly effective μOR-selective receptor agonist makes it unsuitable for analgesia in human, 67,79−81 the radioligand [ 11 C]22 has been approved by the Radioactive Drug Research Committee (RDRC) for use in basic science, 82 is now widely used in clinical PET research, 83 and has played an important role in clinical PET research on movement disorders, 84 pain, 85 emotion, 86,87 and obesity. 29 It is worth mentioning that the human emission systems laboratory in the Nummenmaa [ 11 C]22, while having significant potential, also faced several drawbacks.…”

“…Although the strong potency of CFN as a highly effective μOR-selective receptor agonist makes it unsuitable for analgesia in human, ,− the radioligand [ 11 C] 22 has been approved by the Radioactive Drug Research Committee (RDRC) for use in basic science, is now widely used in clinical PET research, and has played an important role in clinical PET research on movement disorders, pain, emotion, , and obesity . It is worth mentioning that the human emission systems laboratory in the Nummenmaa lab − focused particularly on the study of the endogenous opioid and has made a series of interesting and meaningful studies by combining [ 11 C] 22 PET imaging with advanced signal analysis, large-scale neuroinformatics, and modern clinical pharmacology.…”