Dopamine β-hydroxylase-deficient mice have normal densities of D2 dopamine receptors in the high-affinity state based on in vivo PET imaging and in vitro radioligand binding.

In vitro, D2 dopamine receptors (DAR) can exist in low- and high-affinity states for agonists and increases of D2 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 D2 receptors in a high-affinity state. To determine whether DBH knockout mice display an increase of high-affinity state D2 receptors in vivo, we scanned DBH knockout and control mice with the agonist PET radioligand [11C]MNPA, which is thought to bind preferentially to the high-affinity state of the D2 receptor. In addition, we performed in vitro binding experiments on striatal homogenates with [3H]methylspiperone to measure Bmax values and the percentages of high- and low-affinity states of the D2 receptor. We found that the in vivo striatal binding of [11C]MNPA was similar in DBH knockout mice and heterozygous controls and the in vitro Bmax values and percentages of D2 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 D2 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. [ABSTRACT FROM AUTHOR]