Imaging dopamine D4 receptors in the living primate brain: A positron emission tomography study using the novel D1/ D4 antagonist [11C]SDZ GLC 756
✍ Scribed by Christian Boy; Ansgar Klimke; Marcus Holschbach; Hans Herzog; Heinz Mühlenstepen; Elena Rota Kops; Frank Sonnenberg; Wolfgang Gaebel; Gerhard Stöcklin; Rudolf Markstein; Hans-W. Müller-Gärtner
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 485 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
The dopamine D 4 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 D 4 receptors in primate brain using a [ 11 C]benzo[g]quinoline, the novel radioligand [ 11 C]SDZ GLC 756 ([ 11 C]GLC: in vitro dissociation constants at human receptor clones [nM]: 1.10 at D 1 ; 0.40 at D 2 ; 25 at D 3 ; 0.18 at D 4.2 ; 6.03 at D 5 ). Dynamic positron emission tomography scans were performed on healthy baboons (Papio hamadryas, n ϭ 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 [ 11 C]. Blockade of D 1 and D 5 receptors by SCH23390 (1.7 µmol/kg) diminished SB in the striatum by 55 Ϯ 4% (mean Ϯ standard deviation, P Ͻ 0.05) and in the frontal cortex by 13 Ϯ 8% (P Ͻ 0.05) when compared to SB in the unblocked state (SB D1-D5 ). In the presence of the dopamine antagonists SCH23390 (1.7 µmol/kg) and raclopride (5.7 µmol/kg)-which mask the D 1 , D 2 , D 3 , and D 5 subtypes-SB of [ 11 C]GLC to D 4 receptors (SB D4 ) was demonstrated in the striatum and all cortical regions of interest. In the striatum, the ratio of SB D4 /SB D1-D5 was 0.13 Ϯ 0.07. In the neocortex, SB D4 /SB D1-D5 was notably higher (0.77 Ϯ0.29; mean of all cortical regions of interest). The widespread distribution of dopamine D 4 receptors suggests a basic functional role of this receptor