%0 Journal Article
%A Boy, Christian
%A Klimke, Ansgar
%A Holschbach, Markus
%A Herzog, Hans
%A Mühlensiepen, Heinz
%A Rota Kops, Elena
%A Sonnenberg, Frank
%A Gaebel, Wolfgang
%A Stöcklin, Gerhard
%A Markstein, Rudolf
%A Müller-Gärtner, Hans-W.
%T Imaging Dopamine D4 Receptors in the Living Primate Brain: A Positron Emission Tomography Study Using the Novel D1/D4 Antagonist [11C]SDZ GLC 756
%J Synapse
%V 30
%I Wiley
%M PreJuSER-136190
%P 341–350
%Z Record converted from JUWEL: 18.07.2013
%< Synapse 30:341–350
%X The dopamine D4 receptor has lately attracted interest since it has been
%X 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
%X at D2; 25 at D3; 0.18 at D4.2; 6.03 at D5). Dynamic positron emission tomography scans
%X were performed on healthy baboons (Papio hamadryas, n 5 3). Specific receptor binding
%X (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].
%X Blockade of D1 and D5 receptors by SCH23390 (1.7 μmol/kg) diminished SB in the
%X 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
%X μmol/kg)—which mask the D1, D2, D3, and D5 subtypes—SB of [11C]GLC to D4 receptors
%X (SBD4) was demonstrated in the striatum and all cortical regions of interest. In the
%X striatum, the ratio of SBD4/SBD1–D5 was 0.13 6 0.07. In the neocortex, SBD4/SBD1–D5 was
%X notably higher (0.77 60.29; mean of all cortical regions of interest). The widespread
%X distribution of dopamine D4 receptors suggests a basic functional role of this receptor subtype in the modulation of cortical and subcortical neuronal activity
%F PUB:(DE-HGF)16
%9 Journal Article
%U https://juser.fz-juelich.de/record/136190