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Effects of the A2A adenosine receptor antagonist KW6002 in the nucleus accumbens in vitro and in vivo

Harper, L. K.; Beckett, S. R.; Marsden, C. A.; McCreary, A. C.; Alexander, S. P.H.

Authors

L. K. Harper

S. R. Beckett

C. A. Marsden

A. C. McCreary



Abstract

In this study, we have used the selective A2A adenosine receptor antagonist KW6002 to investigate the function of A2A receptors in the Lister hooded rat nucleus accumbens in vitro and in vivo. Radioligand binding studies confirmed a greater than 50-fold selectivity of KW6002 for A2A receptors compared to A1 receptors. Release of [ 3H]-dopamine from nucleus accumbens slices in vitro was almost doubled in the presence of 300 nM KW6002, while GABA release was inhibited by approximately one third. In vivo, intraperitoneal administration of KW6002 (4 mg kg- 1) increased dopamine overflow almost 4-fold in the nucleus accumbens. In behavioural testing, KW6002 elicited place preference and increased locomotor activity at 1, 2 and 4 mg kg- 1. Taken together, these results suggest a role for tonic activation of A2A adenosine receptors in reward-related phenomena. © 2006 Elsevier Inc. All rights reserved.

Citation

Harper, L. K., Beckett, S. R., Marsden, C. A., McCreary, A. C., & Alexander, S. P. (2006). Effects of the A2A adenosine receptor antagonist KW6002 in the nucleus accumbens in vitro and in vivo. Pharmacology Biochemistry and Behavior, 83(1), 114-121. https://doi.org/10.1016/j.pbb.2005.12.014

Journal Article Type Article
Acceptance Date Dec 20, 2005
Online Publication Date Jan 31, 2006
Publication Date Jan 1, 2006
Deposit Date Dec 3, 2022
Journal Pharmacology Biochemistry and Behavior
Print ISSN 0091-3057
Electronic ISSN 1873-5177
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 83
Issue 1
Pages 114-121
DOI https://doi.org/10.1016/j.pbb.2005.12.014
Public URL https://nottingham-repository.worktribe.com/output/14322259
Publisher URL https://www.sciencedirect.com/science/article/pii/S0091305705004041?via%3Dihub