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Ventral Tegmental Area Cannabinoid Type-1 Receptors Control Voluntary Exercise Performance

  • Sarah Dubreucq
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Audrey Durand
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Isabelle Matias
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Giovanni Bénard
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Elodie Richard
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Edgar Soria-Gomez
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Christelle Glangetas
    Affiliations
    Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5297, Institut Interdisciplinaire de NeuroSciences, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Laurent Groc
    Affiliations
    Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5297, Institut Interdisciplinaire de NeuroSciences, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Aya Wadleigh
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Federico Massa
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Dusan Bartsch
    Affiliations
    Department of Molecular Biology, Central Institute of Mental Health, Mannheim, Germany
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  • Giovanni Marsicano
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Francois Georges
    Affiliations
    Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5297, Institut Interdisciplinaire de NeuroSciences, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
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  • Francis Chaouloff
    Correspondence
    Address correspondence to Francis Chaouloff, PhD, Endocannabinoids and NeuroAdaptation, INSERM U862, NeuroCentre Magendie, 146 rue Léo Saignat, 33077 Bordeaux Cédex, France
    Affiliations
    Institut National de la Santé et de la Recherche Médicale (INSERM) U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France

    Université Bordeaux Segalen, Bordeaux, France
    Search for articles by this author
Published:December 12, 2012DOI:https://doi.org/10.1016/j.biopsych.2012.10.025

      Background

      We have shown that the endogenous stimulation of cannabinoid type-1 (CB1) receptors is a prerequisite for voluntary running in mice, but the precise mechanisms through which the endocannabinoid system exerts a tonic control on running performance remain unknown.

      Methods

      We analyzed the respective impacts of constitutive/conditional CB1 receptor mutations and of CB1 receptor blockade on wheel-running performance. We then assessed the consequences of ventral tegmental area (VTA) CB1 receptor blockade on the wheel-running performances of wildtype (gamma-aminobutyric acid [GABA]-CB1+/+) and mutant (GABA-CB1–/–) mice for CB1 receptors in brain GABA neurons. Using in vivo electrophysiology, the consequences of wheel running on VTA dopamine (DA) neuronal activity were examined in GABA-CB1+/+ and GABA-CB1–/– mice.

      Results

      Conditional deletion of CB1 receptors from brain GABA neurons, but not from several other neuronal populations or from astrocytes, decreased wheel-running performance in mice. The inhibitory consequences of either the systemic or the intra-VTA administration of CB1 receptor antagonists on running behavior were abolished in GABA-CB1–/– mice. The absence of CB1 receptors from GABAergic neurons led to a depression of VTA DA neuronal activity after acute/repeated wheel running.

      Conclusions

      This study provides evidence that CB1 receptors on VTA GABAergic terminals exert a permissive control on rodent voluntary running performance. Furthermore, it is shown that CB1 receptors located on GABAergic neurons impede negative consequences of voluntary exercise on VTA DA neuronal activity. These results position the endocannabinoid control of inhibitory transmission as a prerequisite for wheel-running performance in mice.

      Key Words

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