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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Acknowledgements
This research was supported in part by grants from Spanish Ministerio de Ciencia y Tecnología (SAF2005-00903 to FC and SAF2005-00170 to EIC and SAF2003-04864 and PNSD to RM) and in part by the Intramural Research Program of the National Institutes of Health.
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Carriba, P., Ortiz, O., Patkar, K. et al. Striatal Adenosine A2A and Cannabinoid CB1 Receptors Form Functional Heteromeric Complexes that Mediate the Motor Effects of Cannabinoids. Neuropsychopharmacol 32, 2249–2259 (2007). https://doi.org/10.1038/sj.npp.1301375
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DOI: https://doi.org/10.1038/sj.npp.1301375
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