Sequential versus Nonsequential Measurement of Density and Affinity of Dopamine D2 Receptors with [11C]Raclopride: 2: Effects of DAT Inhibitors

Abstract

The multiple ligand concentration receptor assays (MLCRA) method allows, in a stable condition, reliable and reproducible measurements of the density and affinity of the dopamine (DA) D2 receptors with [11C]raclopride, using either a sequential method (two or more scans in one day) or a nonsequential method (two or more scans over days or weeks). We have shown that measurement of receptor density and affinity is also possible after an acute pharmacological challenge with methamphetamine and that both scanning protocols yield similar values. However, our attempts to measure receptor density and affinity after a pharmacological challenge with another class of drugs that lead to the same outcome, increase in synaptic DA concentrations, revealed opposite results with the two scanning methods: a decrease in receptor density with the sequential method and an increase in affinity with a nonsequential method. These results show the impact of the time-dependency of the effects of an ‘acute’ pharmacological challenge on MLCRA studies. A theoretical simulation is presented to account for the discrepancy in the sequential and nonsequential data. A possible alternate scanning paradigm is proposed to avoid the confounding effect of time variability of the endogenous ligand synaptic concentrations in the sequential condition.