Sequential versus nonsequential measurement of density and affinity of dopamine D2 receptors with [11C]raclopride: 2: effects of DAT inhibitors.
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.
Doudet
Doris J
DJ
Department of Medicine, Division of Neurology and TRIUMF, University of British Columbia, Vancouver, British Columbia, Canada. ddoudet@interchange.ubc.ca
Ruth
Thomas J
TJ
Holden
James E
JE
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology*; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008959:Models, Neurological; D010091:Oximes / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000493:pharmacokinetics*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013997:Time Factors
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D008024:Ligands; D010091:Oximes; D017448:Receptors, Dopamine D2; C415103:brasofensine; D020891:Raclopride; D008694:Methamphetamine