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Dopamine β‐hydroxylase‐deficient mice have normal densities of D 2 dopamine receptors in the high‐affinity state based on in vivo PET imaging and in vitro radioligand binding
Author(s) -
Skinbjerg Mette,
Seneca Nicholas,
Liow JeihSan,
Hong Jinsoo,
Weinshenker David,
Pike Victor W.,
Halldin Christer,
Sibley David R.,
Innis Robert B.
Publication year - 2010
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/syn.20781
Subject(s) - radioligand , receptor , in vivo , knockout mouse , agonist , dopamine , radioligand assay , dopamine receptor , in vitro , chemistry , medicine , endocrinology , biology , biochemistry , microbiology and biotechnology
In vitro, D 2 dopamine receptors (DAR) can exist in low‐ and high‐affinity states for agonists and increases of D 2 receptors in high‐affinity state have been proposed to underlie DA receptor supersensitivity in vivo. Deletion of the gene for dopamine β‐hydroxylase (DBH) causes mice to become hypersensitive to the effects of psychostimulants, and in vitro radioligand binding results suggest an increased percentage of D 2 receptors in a high‐affinity state. To determine whether DBH knockout mice display an increase of high‐affinity state D 2 receptors in vivo, we scanned DBH knockout and control mice with the agonist PET radioligand [ 11 C]MNPA, which is thought to bind preferentially to the high‐affinity state of the D 2 receptor. In addition, we performed in vitro binding experiments on striatal homogenates with [ 3 H]methylspiperone to measure B max values and the percentages of high‐ and low‐affinity states of the D 2 receptor. We found that the in vivo striatal binding of [ 11 C]MNPA was similar in DBH knockout mice and heterozygous controls and the in vitro B max values and percentages of D 2 receptors in the high‐affinity state, were not significantly different between these two groups. In summary, our results suggest that DBH knockout mice have normal levels of D 2 receptors in the high‐affinity state and that additional mechanisms contribute to their behavioral sensitivity to psychostimulants. Synapse 64:699–703, 2010. © 2010 Wiley‐Liss, Inc.