Metabotropic glutamate mGlu5 receptor-mediated modulation of the ventral striopallidal GABA pathway in rats. Interactions with adenosine A(2A) and dopamine D(2) receptors

Neurosci Lett. 2002 May 17;324(2):154-8. doi: 10.1016/s0304-3940(02)00179-9.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Globus Pallidus / cytology
  • Globus Pallidus / drug effects
  • Globus Pallidus / metabolism*
  • Glutamic Acid / metabolism
  • Male
  • Microdialysis
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Phenethylamines / pharmacology
  • Prodrugs
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2A
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Receptors, Purinergic P1 / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Xanthines / pharmacology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Antihypertensive Agents
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • MSX 3 compound
  • Phenethylamines
  • Prodrugs
  • Purinergic P1 Receptor Agonists
  • Purinergic P1 Receptor Antagonists
  • Receptor, Adenosine A2A
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Dopamine D2
  • Receptors, Metabotropic Glutamate
  • Receptors, Purinergic P1
  • Xanthines
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Adenosine