mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine

Adenosine A2A receptors and metabotropic glutamate type 5 (mGlu5) receptors are co-localized in the striatum and can functionally interact to regulate drug-seeking. We further explored this interaction using antagonism of mGlu5 receptors with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) in...

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Bibliographic Details
Published in:The international journal of neuropsychopharmacology 2012-08, Vol.15 (7), p.995-1001
Main Authors: Brown, Robyn M., Duncan, Jhodie R., Stagnitti, Monique R., Ledent, Catherine, Lawrence, Andrew J.
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Autoradiography
Brain - diagnostic imaging
Brain - drug effects
Brain - metabolism
Cocaine - pharmacology
Conditioning, Operant - drug effects
Conditioning, Operant - physiology
Dopamine Uptake Inhibitors - pharmacology
Drug Interactions
Excitatory Amino Acid Antagonists - pharmacology
Iodine Isotopes - pharmacokinetics
Locomotion - drug effects
Locomotion - genetics
Male
Mice
Mice, Knockout
Protein Binding - drug effects
Protein Binding - genetics
Pyridines - pharmacology
Radionuclide Imaging
Receptor, Adenosine A2A - deficiency
Receptor, Adenosine A2A - metabolism
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate - metabolism
Thiazoles - pharmacology
Time Factors
Triazines - pharmacokinetics
Triazoles - pharmacokinetics
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Summary:Adenosine A2A receptors and metabotropic glutamate type 5 (mGlu5) receptors are co-localized in the striatum and can functionally interact to regulate drug-seeking. We further explored this interaction using antagonism of mGlu5 receptors with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) in combination with genetic deletion of A2A receptors. The conditioned rewarding and locomotor-activating properties of cocaine were evaluated via conditioned place preference (CPP). Vehicle-treated mice of both genotypes expressed a CPP to cocaine while MTEP abolished cocaine CPP in wild-type, but not A2A knockout, mice. These results were mirrored when conditioned hyperactivity was assessed. In contrast, MTEP attenuated the acute locomotor-activating properties of cocaine similarly in both genotypes. These data provide evidence for a functional interaction between adenosine A2A and mGlu5 receptors in mediating the conditioned effects of cocaine but not direct cocaine-induced hyperactivity. This functional interaction is supported by modulation of 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP.
ISSN:1461-1457
1469-5111
DOI:10.1017/S146114571100126X