Differential glutamate-dependent and glutamate-independent adenosine A1 receptor-mediated modulation of dopamine release in different striatal compartments

Authors

  • Janusz Borycz,

    1. Department of Health and Human Services, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA
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  • M. Fátima Pereira,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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  • Alessia Melani,

    1. Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy
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  • Ricardo J. Rodrigues,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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  • Attila Köfalvi,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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  • Leigh Panlilio,

    1. Department of Health and Human Services, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA
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  • Felicita Pedata,

    1. Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy
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  • Steven R. Goldberg,

    1. Department of Health and Human Services, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA
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  • Rodrigo A. Cunha,

    1. Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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  • Sergi Ferré

    1. Department of Health and Human Services, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA
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Address correspondence and reprint requests to: Department of Health and Human Services, Sergi Ferré, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
E-mail: sferre@intra.nida.nih.gov

Abstract

Adenosine and dopamine are two important modulators of glutamatergic neurotransmission in the striatum. However, conflicting reports exist about the role of adenosine and adenosine receptors in the modulation of striatal dopamine release. It has been previously suggested that adenosine A1 receptors localized in glutamatergic nerve terminals indirectly modulate dopamine release, by their ability to modulate glutamate release. In the present study, using in vivo microdialysis, we provide evidence for the existence of a significant glutamate-independent tonic modulation of dopamine release in most of the analyzed striatal compartments. In the dorsal, but not in the ventral, part of the shell of the nucleus accumbens (NAc), blockade of A1 receptors by local perfusion with the selective A1 receptor antagonist 8-cyclopentyl-1,3-dimethyl-xanthine or by systemic administration of the non-selective adenosine antagonist caffeine induced a glutamate-dependent release of dopamine. On the contrary, A1 receptor blockade induced a glutamate-independent dopamine release in the core of the NAc and the nucleus caudate–putamen. Furthermore, using immunocytochemical and functional studies in rat striatal synaptosomes, we demonstrate that a fraction of striatal dopaminergic terminals contains adenosine A1 receptors, which directly inhibit dopamine release independently of glutamatergic transmission.

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