Glutamate mGlu5-Adenosine A2A-Dopamine D2 Receptor Interactions in the Striatum. Implications for Drug Therapy in Neuro-psychiatric Disorders and Drug Abuse

Title: Glutamate mGlu5-Adenosine A2A-Dopamine D2 Receptor Interactions in the Striatum. Implications for Drug Therapy in Neuro-psychiatric Disorders and Drug Abuse

Volume: 3 Issue: 1

Author(s): Sergi Ferre, Francisco Ciruela, Amina S. Woods, Meritxell Canals, Javier Burgueno, Daniel Marcellino, Marzena Karcz-Kubicha, Bruce T. Hope, Marisela Morales, Patrizia Popoli, Steven R. Goldberg, Kjell Fuxe, Carme Lluis, Rafael Franco and Luigi Agnati

Affiliation:

Keywords: Dopamine D2 receptor, adenosine A2A receptor, glutamate mGlu5 receptor, striatum, heteromeric receptor complexes, Parkinsons disease, schizophrenia, drug addiction

Abstract: There is growing evidence for the existence of not only homomeric, but also functional heteromeric receptor complexes, particularly involving G protein coupled receptors (GPCRs). These include adenosine A2A-dopamine D2 and adenosine A2A-glutamate mGlu5 receptor complexes. The role of these receptor complexes in receptor function seems to be multiple, involving hetero-modulation of ligand recognition, signalling and trafficking. The preferential localization of A2A-D2 and A2A-mGlu5 receptor complexes is in the dendritic spines of striatopallidal GABAergic neurons. Results obtained from behavioral and in vivo microdialysis experiments have shown an important role of mGlu5-A2A-D2 receptor interactions in the modulation of the function of the striatopallidal GABAergic neurons. The striatopallidal GABAergic neurons play a key role in the pathophysiology of basal ganglia disorders, like Parkinsons disease, and it is a common pathway for the rewarding effects of opiates and psychostimulants and for the antipsychotic effects of neuroleptics. The formation of receptor complexes modifies the single receptor transducing characteristics and leads to the appearance of “emergent properties”. Thus, the study of mGlu5-A2A-D2 receptor interactions in the striatum reveals new properties of these GPCRs and gives indications for a new rational approach for drug therapy in neuro-psychiatric disorders and drug addiction.

Cite this article as:

Ferre Sergi, Ciruela Francisco, Woods S. Amina, Canals Meritxell, Burgueno Javier, Marcellino Daniel, Karcz-Kubicha Marzena, Hope T. Bruce, Morales Marisela, Popoli Patrizia, Goldberg R. Steven, Fuxe Kjell, Lluis Carme, Franco Rafael and Agnati Luigi, Glutamate mGlu5-Adenosine A2A-Dopamine D2 Receptor Interactions in the Striatum. Implications for Drug Therapy in Neuro-psychiatric Disorders and Drug Abuse, Current Medicinal Chemistry - Central Nervous System Agents 2003; 3 (1) . https://dx.doi.org/10.2174/1568015033357779