Effects of the A 2A adenosine receptor antagonist KW6002 in the nucleus accumbens in vitro and in vivo.
In this study, we have used the selective A 2A adenosine receptor antagonist KW6002 to investigate the function of A 2A 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 A 2A 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 A 2A adenosine receptors in reward-related phenomena.
Harper
L K
LK
School of Biomedical Sciences and Institute of Neuroscience, University of Nottingham Medical School, Nottingham, UK.
Beckett
S R
SR
Marsden
C A
CA
McCreary
A C
AC
Alexander
S P H
SP
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000187:drug effects* / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011687:Purines; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; C111599:istradefylline; D005680:gamma-Aminobutyric Acid; C051360:1,3-dipropyl-8-cyclopentylxanthine; D004298:Dopamine