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000136190 041__ $$aEnglish
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000136190 1001_ $$aBoy, Christian$$b0
000136190 245__ $$aImaging Dopamine D4 Receptors in the Living Primate Brain: A Positron Emission Tomography Study Using the Novel D1/D4 Antagonist [11C]SDZ GLC 756
000136190 260__ $$bWiley
000136190 29510 $$aSynapse 30:341–350
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000136190 500__ $$aThe definitive version is available at www3.interscience.wiley.com
000136190 520__ $$aThe dopamine D4 receptor has lately attracted interest since it has been
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
at D2; 25 at D3; 0.18 at D4.2; 6.03 at D5). Dynamic positron emission tomography scans
were performed on healthy baboons (Papio hamadryas, n 5 3). Specific receptor binding
(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].
Blockade of D1 and D5 receptors by SCH23390 (1.7 μmol/kg) diminished SB in the
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
μmol/kg)—which mask the D1, D2, D3, and D5 subtypes—SB of [11C]GLC to D4 receptors
(SBD4) was demonstrated in the striatum and all cortical regions of interest. In the
striatum, the ratio of SBD4/SBD1–D5 was 0.13 6 0.07. In the neocortex, SBD4/SBD1–D5 was
notably higher (0.77 60.29; mean of all cortical regions of interest). The widespread
distribution of dopamine D4 receptors suggests a basic functional role of this receptor subtype in the modulation of cortical and subcortical neuronal activity
000136190 7001_ $$aKlimke, Ansgar$$b1
000136190 7001_ $$aHolschbach, Markus$$b2
000136190 7001_ $$0P:(DE-Juel1)131768$$aHerzog, Hans$$b3
000136190 7001_ $$0P:(DE-Juel1)VDB1101$$aMühlensiepen, Heinz$$b4
000136190 7001_ $$0P:(DE-Juel1)131788$$aRota Kops, Elena$$b5
000136190 7001_ $$aSonnenberg, Frank$$b6
000136190 7001_ $$aGaebel, Wolfgang$$b7
000136190 7001_ $$aStöcklin, Gerhard$$b8
000136190 7001_ $$aMarkstein, Rudolf$$b9
000136190 7001_ $$aMüller-Gärtner, Hans-W.$$b10
000136190 773__ $$0PERI:(DE-600)1474927-0$$p341–350$$tSynapse$$v30$$y1998
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000136190 9201_ $$0I:(DE-Juel1)INM-4-20090406$$kINM-4$$lPhysik der Medizinischen Bildgebung$$x0
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