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

Paulina Carriba, 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

Research output: Contribution to journalArticle

Abstract

The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB 1 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 A 2A 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.

Original languageEnglish (US)
Pages (from-to)2249-2259
Number of pages11
JournalNeuropsychopharmacology
Volume32
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Keywords

  • Adenosine A receptor
  • Cannabinoid CB receptor
  • Cyclic AMP
  • Motor activity
  • Receptor heteromerization
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Carriba, P., Ortiz, O., Patkar, K., Justinova, Z., Stroik, J., Themann, A., Müller, C., Woods, A. S., Hope, B. T., Ciruela, F., Casadó, V., Canela, E. I., Lluis, C., Goldberg, S. R., Moratalla, R., Franco, R., & Ferré, S. (2007). Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology, 32(11), 2249-2259. https://doi.org/10.1038/sj.npp.1301375