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: Johannes Fuss, Jörg Steinle, Laura Bindila, Matthias K Auer, Hartmut Kirchherr, Beat Lutz, Peter Gass
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 112 Issue 42 Pg. 13105-8 (Oct 20 2015) ISSN: 1091-6490 [Electronic] United States
• PMID: 26438875 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2

Topics

• Animals
• Behavior, Animal
• Male
• Mice
• Mice, Inbred C57BL
• Physical Conditioning, Animal
• Receptor, Cannabinoid, CB1 (physiology)
• Receptor, Cannabinoid, CB2 (physiology)
• Running