2. Academic Validation
  3. Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids

Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids

  • Neuropsychopharmacology. 2007 Nov;32(11):2249-59. doi: 10.1038/sj.npp.1301375.
Paulina Carriba 1,  Oskar Ortiz,  Kshitij Patkar,  Zuzana Justinova,  Jessica Stroik,  Andrea Themann,  Christa Müller,  Anima S Woods,  Bruce T Hope,  Francisco Ciruela,  Vicent Casadó,  Enric I Canela,  Carme Lluis,  Steven R Goldberg,  Rosario Moratalla,  Rafael Franco,  Sergi Ferré
Affiliations

Affiliation

  • 1 Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
PMID: 17356572 DOI: 10.1038/sj.npp.1301375
Abstract

The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB1 receptors, is still a matter of debate. In the present study, we report that CB1 and adenosine A2A receptors form heteromeric complexes in co-transfected HEK-293T cells and rat striatum, where they colocalize in fibrilar structures. In a human neuroblastoma cell line, CB1 receptor signaling was found to be completely dependent on A2A receptor activation. Accordingly, blockade of A2A receptors counteracted the motor depressant effects produced by the intrastriatal administration of a cannabinoid CB1 receptor agonist. These biochemical and behavioral findings demonstrate that the profound motor effects of cannabinoids depend on physical and functional interactions between striatal A2A and CB1 receptors.

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