Synapse 2010-09-01

Dopamine beta-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.

Mette Skinbjerg, Nicholas Seneca, Jeih-San Liow, Jinsoo Hong, David Weinshenker, Victor W Pike, Christer Halldin, David R Sibley, Robert B Innis

Index: Synapse 64(9) , 699-703, (2010)

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Abstract

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 beta-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.