In vivo labelling of the adenosine A(2A) receptor in mouse brain using theselective antagonist [H-3]SCH 58261

The selective A(2A) receptor antagonist [H-3]SCH 58261 was injected intrave nously in mice and the radioactivity accumulating in various brain regions was determined by tissue sampling. Radioactivity levels in regions of inter est such as the striatum were highest 15 min after injection and quickly de clined thereafter (30 min and 1 h postinjection) in a time-dependent manner . The amount of labelling was ranked as follows: striatum (4.6 +/-0.3 fmol/ mg protein) >> cortex > hippocampus > pons = hypothalamus > cerebellum (0.5 +/-0.05 fmol/mg protein). Specific labelling of the A(2A) receptor occurre d in striatum and cortex because significantly less radioactivity accumulat ed in these areas from adenosine A(2A) receptor knockout mice as compared t o wild-type littermates. In control outbred CD1 mice, a striatum-to-cerebel lum ratio of 7.6 +/-0.6 was found. At 30 min postinjection, the nonselectiv e adenosine receptor antagonist caffeine reduced the radioactivity due to [ H-3]SCH 58261 in the striatum by 32% at 1 mg/kg i.p. and by 66% at the stim ulant dose of 6.25 mg/kg i.p. Radioactivity in the striatum was lowered, re spectively, by 66 and 86% 30 min after injection of 3 or 10 mg/kg i.p. dose s of unlabelled SCH 58261. The present results indicate that [H-3]SCH 58261 directly labels striatal A(2A) receptors in vivo. Thus [H-3]SCH 58261 is a n excellent tool for studying brain distribution and A(2A) receptor occupan cy of various compounds ranging from xanthines, such as caffeine, to other A(2A) antagonists.