title: A runner's high depends on cannabinoid receptors in mice.
abstract: Exercise is rewarding, and long-distance runners have described a runner's high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner's high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University Medicine Mannheim, University of Heidelberg, 68159 Mannheim, Germany; Institute for Sex Research and Forensic Psychiatry, Center of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; jo.fuss@uke.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Fuss
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University Medicine Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinle
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55099 Mainz, Germany;
authors.forename: Laura
authors.initials: L
authors.lastname: Bindila
authors.affiliation: Department of Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, 80804 Munich, Germany;
authors.forename: Matthias K
authors.initials: MK
authors.lastname: Auer
authors.affiliation: Medizinisches Labor Bremen, 28357 Bremen, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kirchherr
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55099 Mainz, Germany;
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University Medicine Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Gass
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology*; D012420:Running
chemical_list: D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2
keywords: anandamide; anxiety; endocannabinoid; exercise; running