title: Functional role of striatal A2A, D2, and mGlu5 receptor interactions in regulating striatopallidal GABA neuronal transmission.
abstract: In this study, the functional role of individual striatal receptors for adenosine (A2AR), dopamine (D2R), and the metabotropic glutamate receptor mGlu5R in regulating rat basal ganglia activity was characterized in vivo using dual-probe microdialysis in freely moving rats. In particular, intrastriatal perfusion with the D2R agonist quinpirole (10 μM, 60 min) decreased ipsilateral pallidal GABA and glutamate levels, whereas intrastriatal CGS21680 (A2AR agonist; 1 μM, 60 min) was ineffective on either pallidal GABA and glutamate levels or the quinpirole-induced effects. Intrastriatal perfusion with the mGlu5R agonist (RS)-2-chloro-5-hydroxyphenylglycine (600 μM, 60 min), by itself ineffective on pallidal GABA and glutamate levels, partially counteracted the effects of quinpirole. When combined with CGS21680 (1 μM, 60 min), (RS)-2-chloro-5-hydroxyphenylglycine (CHPG; 600 μM, 60 min) fully counteracted the quinpirole (10 μM, 60 min)-induced reduction in ipsilateral pallidal GABA and glutamate levels. These effects were fully counteracted by local perfusion with the mGlu5R antagonist MPEP (300 μM) or the A2AR antagonist ZM 241385 (100 nM). These results suggest that A2ARs and mGlu5Rs interact synergistically in modulating the D2R-mediated control of striatopallidal GABA neurons. Using dual-probe microdialysis, we characterized the functional role of striatal adenosine A2A receptor (A2AR), dopamine D2 receptor (D2R), and metabotropic glutamate receptor 5 (mGluR5) interactions in regulating rat basal ganglia activity. The results suggest the possible usefulness of using an A2AR antagonist and mGluR5 antagonist combination in the treatment of Parkinson's disease to increase the inhibitory D2 signaling on striatopallidal GABA neurons.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.|IRET Foundation, Ozzano Emilia, Bologna, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Beggiato
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.|IRET Foundation, Ozzano Emilia, Bologna, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Tomasini
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Andrea Celeste
authors.initials: AC
authors.lastname: Borelli
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Dasiel Oscar
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: IRET Foundation, Ozzano Emilia, Bologna, Italy.|Department of Medical Sciences, University of Ferrara, Ferrara, Italy.|LTTA Centre, University of Ferrara, Ferrara, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Antonelli
authors.affiliation: IRET Foundation, Ozzano Emilia, Bologna, Italy.|Department of Medical Sciences, University of Ferrara, Ferrara, Italy.|LTTA Centre, University of Ferrara, Ferrara, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Tanganelli
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.|IRET Foundation, Ozzano Emilia, Bologna, Italy.|LTTA Centre, University of Ferrara, Ferrara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D017072:Neostriatum / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; D064529:Receptor, Metabotropic Glutamate 5; D017448:Receptors, Dopamine D2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine
keywords: CGS21680; CHPG; Parkinson's disease; extracellular GABA and glutamate levels; quinpirole; receptor heteromers