Opioid Release after High-Intensity Interval Training in Healthy Human Subjects

Abstract

Central opioidergic mechanisms may modulate the positive effects of physical exercise such as mood elevation and stress reduction. How exercise intensity and concomitant effective changes affect central opioidergic responses is unknown. We studied the effects of acute physical exercise on the cerebral μ-opioid receptors (MOR) of 22 healthy recreationally active males using positron emission tomography (PET) and the MOR-selective radioligand [¹¹C]carfentanil. MOR binding was measured in three conditions on separate days: after a 60-min aerobic moderate-intensity exercise session, after a high-intensity interval training (HIIT) session, and after rest. Mood was measured repeatedly throughout the experiment. HIIT significantly decreased MOR binding selectively in the frontolimbic regions involved in pain, reward, and emotional processing (thalamus, insula, orbitofrontal cortex, hippocampus, and anterior cingulate cortex). Decreased binding correlated with increased negative emotionality. Moderate-intensity exercise did not change MOR binding, although increased euphoria correlated with decreased receptor binding. These observations, consistent with endogenous opioid release, highlight the role of the μ-opioid system in mediating affective responses to high-intensity training as opposed to recreational moderate physical exercise.

Figure 1

Brain regions showing significantly decreased MOR availability after HIIT in comparison with rest. The data are thresholded at p<0.05, false discovery rate corrected. Peak voxels are located in the left hippocampus, coordinates −26, −10, −12 mm (x, y, and z, respectively, in MNI space), cluster size 11098 voxels, T=6.3, Z=4.99; and in the left cerebellum crus II, coordinates −14, −84, −28 mm, cluster size 1922 voxels, T=3.83, Z=3.43. ACC, anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; L, left; MCC, middle cingulate cortex; N, nucleus; OFC, orbitofrontal cortex; PAG, periaqueductal gray matter; PCC, posterior cingulate cortex; PFC, prefrontal cortex; R, right; vSTR, ventral striatum.

Figure 2

Means and standard errors of the means of [¹¹C]carfentanil BP_ND in both statistically significant clusters in each condition. Data include subjects who performed all three scans (rest, MICT, HIIT; n=11) and are shown for visualization purposes only, statistical inference is based on the full-volume SPM analysis.

Figure 3

Means of regional radioactivity concentrations over time in the thalamus (THA), a target region (a), and occipital cortex (OCC), the reference region (b) after injection of [¹¹C]carfentanil. Although changes in both target and reference regions after HIIT suggests altered arterial input function, possibly due to peripheral effects, radioactivity concentration ratios between target and reference regions clearly suggest lower specific uptake after HIIT (c).

Figure 4

Whole brain exploratory analysis revealed that changes in [¹¹C]carfentanil BP_ND predicts increased euphoria after MICT (a) and increased negative affect after HIIT (b). Circles denote the clusters where BP_ND changes are shown against euphoria (a) and negative affect (b) in the scatterplots. Cook’s distance for all observations is<1 suggesting that no single data point or their removal significantly biases the correlation. Peak voxels for euphoria are located in the dorsal prefrontal cortex, coordinates 6, 26, 46 mm (x, y, and z, respectively, in MNI space), cluster size 11039 voxels, T=6.11, Z=4.12; in the medial prefrontal cortex, coordinates 4, 56, 2 mm, cluster size 988 voxels, T=5.43, Z=3.86; and in the precuneus, coordinates 8, −74, 40 mm, cluster size 1499 voxels, T=5.26, Z=3.78. Peak voxel for negative affect is located in the frontal cortex, coordinates 20, 2, 62 mm, cluster size 31066 voxels, T=6.71, Z=3.92.