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.runner's high is described as an ephemeral pleasant phenomenon that may be experienced during long-term running. A popular belief has been that endorphins mediate a runner's high, although neurobiological mechanisms were unclear. In earlier experiments, two prominent systems (the opioid and endocannabinoid systems) were suggested to be involved in a runner's high (1-3). Running increases plasma levels of β-endorphin (an opioid) and anandamide (an endocannabinoid) in mice and men (4, 5). However, unlike the lipophilic anandamide, β-endorphin cannot cross the blood-brain barrier, rendering central effects of peripheral opioids unlikely. In an attempt to disentangle the biomechanism of a runner's high, we were using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, and demonstrated for the first time to our knowledge that a runner's high depends on cannabinoid receptors in mice. Results and DiscussionIn a first step, mice (n = 32) were provided with running wheels for 3 d to start with and to habituate them to wheel running. Mice ran, on average, 5.4 km per day (Fig. 1A). After 2 d with blocked running wheels, half of the mice were assigned into a running (RUN) and the other half to a nonrunning (CON) group, considering matched running distances. Runners (n = 16) were again subjected to a brief period of wheel running (5 h) directly before behavioral testing (day 6) and ran, on average, 6.5 ± 0.7 km (Fig. 1A).When subsequently tested for anxiety-like behavior in the dark-light box test, runners exhibited significantly less anxiety by spending an increased time in the aversive bright area than controls (P = 0.002; Fig. 1B). Runners were also less active and displayed fewer exits from the dark compartment into the lit compartment (RUN, 10.3 ± 0.8 exits; CON, 12.6 ± 0.7 exits; P = 0.040). Next, mice were removed from the dark-light arena and subjected to the hot plate test to study pain sensitivity. Here, runners displayed an increased latency to lick hind paws or jump (first action), suggesting reduced thermal pain sensitivity (P = 0.0...

Endocannabinoid concentrations in hair are associated with PTSD symptom severity

“…Exercise has also been shown to improve symptoms in PTSD patients (Rosenbaum et al, 2015b). Interestingly, physical exercise increases peripheral endocannabinoid concentrations in humans (Feuerecker et al, 2012) and endocannabinoid receptors mediate anxiolysis and pain reduction in mice after exercise (Fuss et al, 2015). In sum, the negative, dose-dependent relationship between PTSD symptom severity and N-acyl-ethanolamides might contribute to the explanation of the association between PTSD symptoms and inflammation, increased cardiovascular risk and the metabolic syndrome.…”

The ‘physiologization’ of skiing: the lab as an obligatory passage point for elite athletes?

“…Research on endogenous human substances of morphine character, such as dopamine or endorphin, developed in the 1970s (cf. Terenius 1973;Snell 1978), and, more recently on cannabinoids (Fuss et al 2015) have become much used in the narrative cultures of endurance sports and lended an aura of science to physiological experience. Perhaps it would be useful to think of not only competitive elite sports as undergoing a physiologization.…”

Nascidos Para Correr: A Importância Do Exercício Para a Saúde Do Cérebro

“…No entanto, é improvável que esse aumento de ativação resulte em excitotoxidade associada ao glutamato, já que o exercício também eleva os níveis de proteínas neuroprotetoras como o BDNF 25 . Outros fatores neuroquímicos liberados durante o exercício agudo incluem o aumento na síntese de opióides e endocanabinóides, responsáveis pela sensação de euforia, bem-estar, sedação e redução à sensibilidade da dor [31][32][33][34][35][36][37] . Além disso, agonistas externos exógenos, como a morfina e a heroína, suprimem a neurogênese in vivo 31,32 , enquanto, endorfinas e encefalinas estimulam a gênese celular in vitro [33][34][35] .…”

“…Outros estudos em animais mostraram ainda que o sistema endocanabinóide pode ter um papel relevante na sensação de sedação e bem estar após o exercício, conhecida como "onda de corredor" 37 . As endorfinas não atravessam a barreira hematoencefálica, mas a molécula lipossolúvel da anandamida, um endocanabinóide, pode entrar no cérebro e desencadear as conhecidas sensações.…”