Ventral tegmental area cannabinoid type-1 receptors control voluntary exercise performance.
Biological Psychiatry. 2013-05-01; 73(9): 895-903
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1. Biol Psychiatry. 2013 May 1;73(9):895-903. doi: 10.1016/j.biopsych.2012.10.025.
Epub 2012 Dec 11.
Ventral tegmental area cannabinoid type-1 receptors control voluntary exercise
Dubreucq S(1), Durand A, Matias I, Bénard G, Richard E, Soria-Gomez E, Glangetas
C, Groc L, Wadleigh A, Massa F, Bartsch D, Marsicano G, Georges F, Chaouloff F.
(1)Institut National de la Santé et de la Recherche Médicale-INSERM, U862,
NeuroCentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux,
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⁻/⁻
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.
Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All
PMID: 23237313 [Indexed for MEDLINE]