Adenosine A2A receptors enable the synaptic effects of cannabinoid CB1 receptors in the rodent striatum

Authors

  • Maria Teresa Tebano,

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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  • Alberto Martire,

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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  • Valentina Chiodi,

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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  • Rita Pepponi,

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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  • Antonella Ferrante,

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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  • Maria Rosaria Domenici,

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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  • Claudio Frank,

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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  • Jiang-Fan Chen,

    1. Department of Neurology, Boston University School of Medicine, Boston, MA, USA
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  • Catherine Ledent,

    1. Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Université Libre de Bruxelles, Bruxelles, Belgium
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  • Patrizia Popoli

    1. Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
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Address correspondence and reprint requests to M. T. Tebano, Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. E-mail: mariateresa.tebano@iss.it

Abstract

Adenosine A2A, cannabinoid CB1 and metabotropic glutamate 5 (mGlu5) receptors are all highly expressed in the striatum. The aim of the present work was to investigate whether, and by which mechanisms, the above receptors interact in the regulation of striatal synaptic transmission. By extracellular field potentials (FPs) recordings in corticostriatal slices, we demonstrated that the ability of the selective type 1 cannabinoid receptor (CB1R) agonist WIN55,212-2 to depress synaptic transmission was prevented by the pharmacological blockade or the genetic inactivation of A2ARs. Such a permissive effect of A2ARs towards CB1Rs does not seem to occur pre-synaptically as the ability of WIN55,212-2 to increase the R2/R1 ratio under a protocol of paired-pulse stimulation was not modified by ZM241385. Furthermore, the effects of WIN55,212-2 were reduced in slices from mice lacking post-synaptic striatal A2ARs. The selective mGlu5R agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) potentiated the synaptic effects of WIN55,212-2, and such a potentiation was abolished by A2AR blockade. Unlike the synaptic effects, the ability of WIN55,212-2 to prevent NMDA-induced toxicity was not influenced by ZM241385. Altogether, these results show that the state of activation of A2ARs regulates the synaptic effects of CB1Rs and that A2ARs may control CB1 effects also indirectly, namely through mGlu5Rs.

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