TY - JOUR AU - Boy, Christian AU - Klimke, Ansgar AU - Holschbach, Markus AU - Herzog, Hans AU - Mühlensiepen, Heinz AU - Rota Kops, Elena AU - Sonnenberg, Frank AU - Gaebel, Wolfgang AU - Stöcklin, Gerhard AU - Markstein, Rudolf AU - Müller-Gärtner, Hans-W. TI - Imaging Dopamine D4 Receptors in the Living Primate Brain: A Positron Emission Tomography Study Using the Novel D1/D4 Antagonist [11C]SDZ GLC 756 JO - Synapse VL - 30 PB - Wiley M1 - PreJuSER-136190 SP - 341–350 N1 - Record converted from JUWEL: 18.07.2013 AB - The dopamine D4 receptor has lately attracted interest since it has been AB - hypothesized to be involved in the pathogenesis and pharmacotherapy of neuropsychiatric diseases. The present study provides first in vivo evidence of dopamine D4 receptors in primate brain using a [11C]benzo[g]quinoline, the novel radioligand [11C]SDZ GLC 756 ([11C]GLC: in vitro dissociation constants at human receptor clones [nM]: 1.10 at D1; 0.40 AB - at D2; 25 at D3; 0.18 at D4.2; 6.03 at D5). Dynamic positron emission tomography scans AB - were performed on healthy baboons (Papio hamadryas, n 5 3). Specific receptor binding AB - (SB) was calculated for striatum and neocortex (frontal, temporal, parietal, and occipital) based on the differences between the regional and the cerebellar concentration of [11C]. AB - Blockade of D1 and D5 receptors by SCH23390 (1.7 μmol/kg) diminished SB in the AB - striatum by 55 6 4% (mean 6 standard deviation, P , 0.05) and in the frontal cortex by 13 6 8% (P , 0.05) when compared to SB in the unblocked state (SBD1–D5). In the presence of the dopamine antagonists SCH23390 (1.7 μmol/kg) and raclopride (5.7 AB - μmol/kg)—which mask the D1, D2, D3, and D5 subtypes—SB of [11C]GLC to D4 receptors AB - (SBD4) was demonstrated in the striatum and all cortical regions of interest. In the AB - striatum, the ratio of SBD4/SBD1–D5 was 0.13 6 0.07. In the neocortex, SBD4/SBD1–D5 was AB - notably higher (0.77 60.29; mean of all cortical regions of interest). The widespread AB - distribution of dopamine D4 receptors suggests a basic functional role of this receptor subtype in the modulation of cortical and subcortical neuronal activity LB - PUB:(DE-HGF)16 UR - https://juser.fz-juelich.de/record/136190 ER -