The runner's high describes a euphoric state resulting from long-distance running. The cerebral neurochemical correlates of exercise-induced mood changes have been barely investigated so far. We aimed to unravel the opioidergic mechanisms of the runner's high in the human brain and to identify the relationship to perceived euphoria. We performed a positron emission tomography "ligand activation" study with the nonselective opioidergic ligand 6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([(18)F]FDPN). Ten athletes were scanned at 2 separate occasions in random order, at rest and after 2 h of endurance running (21.5 +/- 4.7 km). Binding kinetics of [(18)F]FDPN were quantified by basis pursuit denoising (DEPICT software). Statistical parametric mapping (SPM2) was used for voxelwise analyses to determine relative changes in ligand binding after running and correlations of opioid binding with euphoria ratings. Reductions in opioid receptor availability were identified preferentially in prefrontal and limbic/paralimbic brain structures. The level of euphoria was significantly increased after running and was inversely correlated with opioid binding in prefrontal/orbitofrontal cortices, the anterior cingulate cortex, bilateral insula, parainsular cortex, and temporoparietal regions. These findings support the "opioid theory" of the runner's high and suggest region-specific effects in frontolimbic brain areas that are involved in the processing of affective states and mood.

Essential tremor is the most common movement disorder, but the underlying pathophysiology is not well understood. A primary overactivity of cerebellothalamic output pathways is the most conspicuous finding, as indicated by animal and human studies. It has been argued that this overactivity may be due to impaired central inhibition, and converging evidence points toward a potential role of gamma-aminobutyric acid (GABA) dysfunction in tremor generation. Using (11)C-flumazenil and PET, we calculated the distribution volume, an index of availability of benzodiazepine receptor sites of the GABA(A) complex, in a group of 8 patients with bilateral essential tremor, as compared with 11 healthy controls. Significant increases in binding of (11)C-flumazenil at the benzodiazepine receptor site of the GABA(A) receptor in the cerebellum, the ventrolateral thalamus, and the lateral premotor cortex were identified in the essential tremor group. Essential tremor is associated with reduced GABAergic function and increased availability of benzodiazepine receptor sites in brain regions implicated specifically in tremor genesis. This finding is thought to reflect overactivity of cerebellothalamic circuits and, hence, lends support to the "GABA hypothesis" of essential tremor.

Background: The phenomenon of exercise‐induced hypoalgesia and concomitant mood changes is well‐established. How exercise‐induced hypoalgesia and affective responses are shaped by the intensity of an acute exercise bout and individual fitness levels is as yet not well‐understood. This study investigates whether heat pain threshold (PTh), pain tolerance (PTol) and affective parameters are modulated by the intensity of an acute exercise bout and/or individuals’ fitness level. Stronger analgesic responses are hypothesized after high‐intensity exercise in physically fitter subjects, possibly in sync with concomitant mood changes.Methods: Thirty‐three healthy men were recruited (sedentary: N = 17 or recreational: N = 14; mean age: 25.3 ± 4.4 years). After a fitness assessment on a cycle ergometer, subjects underwent three experimental conditions on separate days: high (20 min exercise 20% above lactate threshold), low (20 min exercise 20% below lactate threshold) and control (seated rest). Before and after each intervention Positive and Negative Affect Schedule, PTh and PTol (cold water emersion test) were assessed.Results: Results indicate an increase of the Positive Affect Scale (high: 26.7 ± 9.0 vs. 32.9 ± 7.1, p < .001; low: 26.3 ± 7.2 vs. 32.0 ± 7.0, p < .001) and PTh (high: 45.1 ± 3.1°C vs. 46.0 ± 2.6°C, p = .003; low: 45.4 ± 2.7°C vs. 45.9 ± 2.6°C, p = .012) after both exercise conditions. In an exploratory analysis, PTol significantly increased only after the high exercise condition (51.2 ± 33.7 s vs. 72.4 ± 64.0 s, p = .045). Fitness level was positively correlated with the increase in PTol from pre to post high‐intensity exercise (r = .59, p (one‐tailed) = .002).Conclusion: Exercise‐induced hypoalgesia depends on exercise intensity and appears to be influenced by individual fitness status, independent of mood responses.Significance: Antinociceptive effects can be elicited by physical exercise and have been extensively investigated in the literature. However, the relation between exercise intensity, fitness status, and the degree of antinociception is not well‐understood. This randomized intervention provides novel evidence that antinociceptive effects indeed depend on exercise intensity, but also on general fitness status. Data extend the existing literature by highlighting aspects of exercise behaviour that promote antinociception. Effects do not simply mirror positive affective responses induced by exercise, hence, indicating partially distinct underlying mechanisms.