Abstract
Interactions between subtypes of dopamine, glutamate and adenosine receptors seem to play an important integrative role in the function of striatal gamma-aminobutyric acid (GABA)ergic efferent neurons. Recent behavioral and biochemical studies suggest the existence of specific interactions between adenosine A2A receptors (A(2A)R), dopamine D2 receptors (D2R) and the group I metabotropic mGlu5 receptors (mGlu5R) in the dorsal striatum. The dual-probe approach in vivo microdialysis technique in freely moving rats was used to study the role of mGlu5R/A2AR/D2R interactions in the modulation of the ventral striopallidal GABA pathway. Perfusion of a selective mGlu5R agonist (CHPG) in the nucleus accumbens facilitated GABA release in the ipsilateral ventral pallidum. This effect was strongly potentiated by co-perfusion with the A2AR agonist CGS 21680. Co-perfusion with the D2R agonist quinpirole counteracted the increase in pallidal GABA levels induced by CGS 21680 and by CGS 21680 plus CHPG. These results demonstrate that mGlu5R/A2AR/D2R interactions play an important modulatory role in the function of the ventral striopallidal GABA pathway, which might have implications for the treatment of schizophrenia and drug addiction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / pharmacology
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Animals
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Antihypertensive Agents / pharmacology
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Extracellular Space / drug effects
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Extracellular Space / metabolism
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Globus Pallidus / cytology
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Globus Pallidus / drug effects
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Globus Pallidus / metabolism*
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Glutamic Acid / metabolism
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Male
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Microdialysis
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Neural Inhibition / drug effects
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Neural Inhibition / physiology
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Neural Pathways / cytology
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Neural Pathways / drug effects
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Neural Pathways / metabolism*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Nucleus Accumbens / cytology
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Nucleus Accumbens / drug effects
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Nucleus Accumbens / metabolism*
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Phenethylamines / pharmacology
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Prodrugs
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Purinergic P1 Receptor Agonists
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Purinergic P1 Receptor Antagonists
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Rats
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Rats, Sprague-Dawley
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Receptor, Adenosine A2A
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Receptor, Metabotropic Glutamate 5
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Receptors, Dopamine D2 / drug effects
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Receptors, Dopamine D2 / metabolism*
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Receptors, Metabotropic Glutamate / agonists
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / metabolism*
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Receptors, Purinergic P1 / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Xanthines / pharmacology
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gamma-Aminobutyric Acid / metabolism*
Substances
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Antihypertensive Agents
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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MSX 3 compound
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Phenethylamines
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Prodrugs
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Purinergic P1 Receptor Agonists
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Purinergic P1 Receptor Antagonists
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Receptor, Adenosine A2A
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Receptor, Metabotropic Glutamate 5
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Receptors, Dopamine D2
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Receptors, Metabotropic Glutamate
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Receptors, Purinergic P1
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Xanthines
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2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
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Glutamic Acid
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gamma-Aminobutyric Acid
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Adenosine