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Imaging dopamine D 4 receptors in the living primate brain: A positron emission tomography study using the novel D 1 / D 4 antagonist [ 11 C]SDZ GLC 756
Author(s) -
Boy Christian,
Klimke Ansgar,
Holschbach Marcus,
Herzog Hans,
Mühlenstepen Heinz,
Kops Elena Rota,
Sonnenberg Frank,
Gaebel Wolfgang,
Stöcklin Gerhard,
Markstein Rudolf,
MüllerGärtner HansW.
Publication year - 1998
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199812)30:4<341::aid-syn1>3.0.co;2-6
Subject(s) - dopamine , striatum , raclopride , neocortex , radioligand , medicine , temporal cortex , dopamine receptor , dopamine receptor d3 , dopamine receptor d2 , dopamine receptor d1 , receptor , neuroscience , chemistry , endocrinology , human brain , positron emission tomography , pharmacology , psychology , biology
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 = 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 ± 4% (mean ± standard deviation, P < 0.05) and in the frontal cortex by 13 ± 8% ( P < 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 ± 0.07. In the neocortex, SB D4 / SB D1–D5 was notably higher (0.77 ±0.29; mean of all cortical regions of interest). The widespread distribution of dopamine D 4 receptors suggests a basic functional role of this receptor subtype in the modulation of cortical and subcortical neuronal activity. Synapse 30:341–350, 1998. © 1998 Wiley‐Liss, Inc.