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

JCI Insight. 2019 Mar 7;4(5):e126190. doi: 10.1172/jci.insight.126190.

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.

Keywords: Behavior; Neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Conditioning, Operant
  • Dopamine Agents
  • Feeding Behavior
  • Haloperidol / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Motivation / physiology*
  • Physical Conditioning, Animal*
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Running

Substances

  • Dopamine Agents
  • Receptor, Cannabinoid, CB1
  • Haloperidol

Grants and funding

This work was supported by Institut National de la Santé et de la Recherche Médicale (to GM), la Région Aquitaine (to Dr Giovanni Marsicano; GM), the University of Bordeaux (to GM), the European Research Council (to GM), l’Agence Nationale de la Recherche (to GM and Dr Francois Georges), l’Agence Française de Lutte contre le Dopage (to Dr Francis Chaouloff; FC), the LabEx-Bordeaux Région Aquitaine Initiative for Neuroscience (to GM, FC and FG), and the Government of the Basque Country (to Dr Carolina Muguruza and FC).