title: Ventral tegmental area cannabinoid type-1 receptors control voluntary exercise performance.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale-INSERM, U862, NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dubreucq
authors.forename: Audrey
authors.initials: A
authors.lastname: Durand
authors.forename: Isabelle
authors.initials: I
authors.lastname: Matias
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bénard
authors.forename: Elodie
authors.initials: E
authors.lastname: Richard
authors.forename: Edgar
authors.initials: E
authors.lastname: Soria-Gomez
authors.forename: Christelle
authors.initials: C
authors.lastname: Glangetas
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
authors.forename: Aya
authors.initials: A
authors.lastname: Wadleigh
authors.forename: Federico
authors.initials: F
authors.lastname: Massa
authors.forename: Dusan
authors.initials: D
authors.lastname: Bartsch
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Francois
authors.initials: F
authors.lastname: Georges
authors.forename: Francis
authors.initials: F
authors.lastname: Chaouloff
mesh_terms: D000818:Animals; D013759:Dronabinol / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D013759:Dronabinol; D000077285:Rimonabant