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Cerebral Cortex Advance Access published online on February 21, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn013
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

The Runner's High: Opioidergic Mechanisms in the Human Brain

Henning Boecker1,2, Till Sprenger3, Mary E. Spilker1, Gjermund Henriksen1, Marcus Koppenhoefer1, Klaus J. Wagner4, Michael Valet3, Achim Berthele3 and Thomas R. Tolle3

1 Nuklearmedizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany, 2 Radiologische Universitätsklinik, FE Klinische Funktionelle Neurobildgebung, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany, 3 Neurologische Klinik, 4 Klinik für Anaesthesiologie, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany

Address correspondence to email: henning.boecker{at}ukb.uni-bonn.de.

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-[18F]fluoroethyl)-6-O-desmethyldiprenorphine ([18F]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 [18F]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.

Key Words: emotion • exercise • ligand activation • limbic system • opioid • PET (positron emission tomography) • prefrontal • runner's high


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