mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine |
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Authors: | Brown Robyn M Duncan Jhodie R Stagnitti Monique R Ledent Catherine Lawrence Andrew J |
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Institution: | Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria, Australia. |
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Abstract: | 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]triazolol2,3-a]1,3,5]triazin-5-yl-amino]ethyl)phenol (125I]ZM241385) binding to the A2A receptor by MTEP. |
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