The motivation for exercise over palatable food is dictated by cannabinoid type-1 receptors
Carolina Muguruza, Bastien Redon, Giulia R. Fois, Imane Hurel, Amandine Scocard, Claire Nguyen, Christopher Stevens, Edgar Soria-Gomez, Marjorie Varilh, Astrid Cannich, Justine Daniault, Arnau Busquets-Garcia, Teresa Pelliccia, Stéphanie Caillé, François Georges, Giovanni Marsicano, Francis Chaouloff
Carolina Muguruza, Bastien Redon, Giulia R. Fois, Imane Hurel, Amandine Scocard, Claire Nguyen, Christopher Stevens, Edgar Soria-Gomez, Marjorie Varilh, Astrid Cannich, Justine Daniault, Arnau Busquets-Garcia, Teresa Pelliccia, Stéphanie Caillé, François Georges, Giovanni Marsicano, Francis Chaouloff
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Research Article Neuroscience

The motivation for exercise over palatable food is dictated by cannabinoid type-1 receptors

Abstract

The lack of intrinsic motivation to engage in, and adhere to, physical exercise has major health consequences. However, the neurobiological bases of exercise motivation are still unknown. This study aimed at examining whether the endocannabinoid system (ECS) is involved in this process. To do so, we developed an operant conditioning paradigm wherein mice unlocked a running wheel with nose pokes. Using pharmacological tools and conditional mutants for cannabinoid type-1 (CB1) receptors, we provide evidence that CB1 receptors located on GABAergic neurons are both necessary and sufficient to positively control running motivation. Conversely, this receptor population proved dispensable for the modulation of running duration per rewarded sequence. Although the ECS mediated the motivation for another reward, namely palatable food, such a regulation was independent from CB1 receptors on GABAergic neurons. In addition, we report that the lack of CB1 receptors on GABAergic neurons decreases the preference for running over palatable food when mice were proposed an exclusive choice between the two rewards. Beyond providing a paradigm that enables motivation processes for exercise to be dissected either singly or in concurrence, this study is the first to our knowledge to identify a neurobiological mechanism that might contribute to sedentary behavior.

Authors

Carolina Muguruza, Bastien Redon, Giulia R. Fois, Imane Hurel, Amandine Scocard, Claire Nguyen, Christopher Stevens, Edgar Soria-Gomez, Marjorie Varilh, Astrid Cannich, Justine Daniault, Arnau Busquets-Garcia, Teresa Pelliccia, Stéphanie Caillé, François Georges, Giovanni Marsicano, Francis Chaouloff

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Figure 5

CB1 receptors on GABAergic neurons gate the motivation for running over palatable food in ad libitum–fed mice and food-restricted mice.

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CB1 receptors on GABAergic neurons gate the motivation for running over ...
(A) Operant chamber set up with active/inactive nose poke (aNP/iNP) ports. (B) Fed, but not food-restricted, CB1-WT mice (n = 10) displayed more aNP for wheel running than for food during fixed ratio 3 (FR3) choice sessions. (C) Fed and food-restricted CB1-KO mice (n = 6) performed fewer aNP for wheel running than for food during choice sessions. (D) Preference scores for wheel running were lower in CB1-KO mice than in CB1-WT mice. (E) Fed, but not food-restricted, GABA-CB1-WT mice (n = 8) displayed more aNP for wheel running than for food during choice sessions. (F) Fed and food-restricted GABA-CB1-KO mice (n = 12) performed fewer aNP for wheel running than for food under FR3 schedules of reinforcement. (G) Preference scores for wheel running were lower in GABA-CB1-KO mice than in GABA-CB1-WT mice under fed and food-restricted conditions. (H and I) Fed, but not food-restricted, Glu-CB1-WT mice (n = 5) and Glu-CB1-KO mice (n = 5) displayed more aNP for wheel running than for food during choice sessions. (J) Preference scores for wheel running were similar in Glu-CB1-WT and Glu-CB1-KO mice. Data represent mean ± SEM. *P < 0.05, **P < 0.01 for comparisons between wheel and food (performed by Tukey’s test if the 2-way ANOVA provided significant variable interaction; B, E, H, and I) and for main significance in the 2-way ANOVA between the rewards (C, D, F, and G). +P < 0.05, ++P < 0.01 for comparisons between wheel preference scores and nonpreference (50%) by 1-tailed Student’s t tests (D, G, and J).