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MGlu5 and adenosine A 2A receptor interactions regulate the conditioned effects of cocaine

par Brown, Robyn Mary Ary R.M.;Duncan, Jhodie Rubina;Stagnitti, Monique M.R.;Lawrence, Andrew John;Ledent, Catherine
Référence International journal of neuropsychopharmacology, 15, 7, page (995-1001)
Publication Publié, 2012-08

Article révisé par les pairs

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Résumé :

Adenosine A 2A 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 A 2A 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 A 2A 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 A 2A 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 A 2A receptor by MTEP. © 2011 CINP.