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 2

CB1 receptors control running motivation.

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CB1 receptors control running motivation. (A) Active/inactive nose poke ...
(A) Active/inactive nose poke (aNP/iNP) performed by C57BL/6N mice during the acquisition phase of conditioned wheel running (n = 39). (B and C) Intraperitoneal administration of SR141716 (n = 12 vs. n = 12 for vehicle; B) or O-2050 (n = 8 vs. n = 7 for vehicle; C) prior to a progressive ratio (PR) session (session 13) decreased the maximal performance of aNP but not the running duration per sequence (n = 5 for that variable in O-2050–treated mice). (D and E) CB1-KO mice (n = 7) displayed fewer aNP, but not a defective running performance per sequence, compared with their WT littermates (n = 9). (F) aNP responses, but not the running duration per sequence, were reduced in CB1-KO mice (n = 6) tested under a PR schedule of reinforcement (session 13), compared with WT littermates (n = 13). (G) Schematic illustration of the bilateral infusion of the CB1 receptor antagonist AM251 in the ventral tegmental area (VTA) of C57BL/6N mice, with an image of a coronal section showing the injection sites. (H) NP responses before and after VTA cannula implantation in C57BL/6N mice (n = 24). (I) Intra-VTA infusion of AM251 decreases the maximal number of aNP performed during the PR session (n = 10), but not the running duration per rewarded sequence (n = 4), compared with vehicle-perfused mice (n = 14 and n = 10 for each variable, respectively). Data represent mean ± SEM. *P < 0.05, **P < 0.01 for 2-group comparisons by Student’s t tests (B, C, F, and I) and for overall genotype differences in 2-way ANOVA (D). Scale bar: 2 mm (G).