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 1

The rewarding effect of conditioned wheel running is linked to dopaminergic activity.

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The rewarding effect of conditioned wheel running is linked to dopaminer...
(A) Operant chamber set up with active/inactive nose poke (aNP/iNP) ports. (B–D) NP performed by CB1-WT mice during fixed ratio (FR) and extinction sessions and during a cue-induced reinstatement session (n = 10). (E) NP performed by C57BL/6N mice during the acquisition phase of conditioned wheel running (n = 34). (F) Intraperitoneal administration of haloperidol (n = 9 at 0.15 mg/kg haloperidol and n = 10 at 0.3 mg/kg haloperidol vs. n = 15 for vehicle) prior to a progressive ratio (PR) session (session 13) decreased the maximal performance of aNP but not the running duration per sequence. (G) Chamber set-up protocol in C57BL/6N mice that distinguishes the respective effects of (a) the exposure to operant chambers with inactive wheels (controls; n = 6), (b) wheel running elicited by prior aNP performance (operant; n = 10), and (c) wheel running elicited by prior aNP performance of an operant congener (yoked mouse; n = 12). (H) aNP/iNP performed by the operant mice (n = 10) and duration of wheel running in operant and yoked mice (n = 12) during FR/PR sessions. (I) Schematic illustration of the electrophysiological recording of VTA dopaminergic neurons with representative electrophysiologic traces of these neurons in control mice, in weakly (low PR) and highly (high PR) motivated operant mice, and in yoked mice. (J) Relationship between the number of aNP performed during the PR session and the firing rate of VTA dopaminergic neurons in operant mice. (K) Lack of relationship between running duration during the PR session and the firing rate of VTA dopaminergic neurons in yoked mice. Data represent mean ± SEM. **P < 0.01 for 2-group comparisons by Student’s t tests (D) and for multiple-group comparisons performed by Tukey’s test when 1-way ANOVA provided significant variable interaction (F) In J and K, P values were obtained by 1-way ANOVA for regression lines; the numbers above/below means refer to the numbers of recorded neurons per mouse. Numbers above/below means refer to the numbers of recorded neurons per mouse (J and K). Scale bar: 1 second (I).