Autoradiographic studies in adenosine A 1 and A 2A receptor knockout (KO) mice (Johansson et al, 2001, PNAS, 98, 9407; Ledent et al., 1997, Nature, 388, 624) indicated that the binding of the purportedly A 2A receptor selective agonist CGS21680 in the hippocampus is not only to an A 2A receptor, but requires the presence of A 1 receptors (Fredholm et al, 2001, SFN proceeds.). We now confirmed and extended these observations. Saturation binding curves were performed using the selective A 1 antagonist, [3H]DPCPX and the A 2A agonist[3H]CGS21680 in membranes from different mice brain regions. The A 1-KO mice displayed a non detectable binding of [3H]DPCPX(0.1-10 nM) in the hippocampus, striatum and cortex, in contrast to wild type mice (WT) which displayed Bmax values ranging from 4196(3497-4896) to 1747(1399-2095) fmol/mg protein. However, in A 1-KO mice, we observed no detectable binding of [3H]CGS21680(0.1 to 20 nM) to the hippocampus and a lower binding in the cortex. Also, [3H]CGS21680 binding in the hip...