High-intensity interval training exercise decreases brain CB1 receptor levels in male and female adult rats

The numerous health benefits of exercise are well-documented, including its efficacy in treating substance use disorders (SUDs). Several exercise regimens have been proposed; however, the most effective regimen for patients with addiction has yet to be elucidated. High-intensity interval training (HIIT) exhibits considerable potential compared to aerobic and resistance exercise. Dopamine signaling is recognized as a key neurobiological mechanism contributing to HIIT's therapeutic potential for SUDs; however, the role of the endocannabinoid system in this context is not well understood. The present study investigated the effects of HIIT exercise on endocannabinoid signaling by measuring cannabinoid receptor 1 (CB1R) binding in the brains of male and female rats using [³H] SR141716A autoradiography. Male and female rats were separated into sedentary and HIIT exercise groups. For six weeks, exercise was completed daily on a treadmill for 30 min (10 3-min intervals) progressively increasing speed to 0.8 mph (21.5 m/min). The HIIT program significantly reduced CB1R binding in both sexes across multiple brain regions, including the striatum, thalamus, and distinct areas of the cortex. Sex differences were observed wherein males exhibited greater CB1R binding than females across brain regions, including the cerebellum, striatum, and parts of the cortex. Males experienced an increase in mean cerebellum CB1R binding due to HIIT, whereas females showed no effect in this region. The results suggest HIIT exercise can modulate endocannabinoid signalling by way of decreased CB1R binding. These findings further support the intensity dependence of endocannabinoid modulation and highlight potential pathways for exercise-induced neurobiological and behavioural change.