期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 15, 期 7, 页码 995-1001出版社
OXFORD UNIV PRESS
DOI: 10.1017/S146114571100126X
关键词
Cocaine; conditioned place preference; heteromer; mGlu5 receptor; receptor interactions
资金
- National Health & Medical Research Council of Australia [566736]
- Pratt Foundation
- Besen Foundation
- Victorian Government's Operational Infrastructure Support Program
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 ([I-125]ZM241385) binding to the A(2A) receptor by MTEP.
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