The International Journal of Neuropsychopharmacology
- The International Journal of Neuropsychopharmacology / Volume 15 / Issue 07 / August 2012, pp 995-1001
- © CINP 2011
- DOI: http://dx.doi.org/10.1017/S146114571100126X (About DOI), Published online: 05 August 2011
Brief Report
mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine
Robyn M. Browna1, Jhodie R. Duncana1a2, Monique R. Stagnittia1, Catherine Ledenta4 and Andrew J. Lawrencea1a3 c1
a1 Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria, Australia
a2 Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia
a3 Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia
a4 Institut de Recherche Interdisciplinaire, Faculté de Médecine, Université de Bruxelles, Brussels, Belgium
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]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP.
(Received February 28 2011)
(Reviewed March 24 2011)
(Revised July 03 2011)
(Accepted July 09 2011)
(Online publication August 05 2011)
Correspondence:
c1 Address for correspondence: Professor A. J. Lawrence, Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria 3010, Australia. Tel.: +613 8344 0414 Fax: +613 9348 1707 Email: andrew.lawrence@florey.edu.au
