Oral D-amphetamine causes prolonged displacement of [11C]raclopride as measured by PET

Parenterally administered D-amphetamine has been used as a challenge drug to release dopamine, which in turns inhibits [C-11]raclopride binding to dopaminergic D-2 receptors as measured using positron emission tomography (PET) techniques. The primary objective of this study was to determine whether orally administered D-amphetamine would inhibit [C-11]raclopride binding in a manner similar to that produced by intravenously administered D-amphetamine. The secondary objective was to assess the timeline of these effects. Twelve healthy human volunteers participated in this study. Subjects were scanned at baseline and 2 h after D-amphetamine administration (n = 5); at baseline, 2 and 6 h postdrug (n = 4); or at baseline, 2 and 24 h postdrug (n = 3). Orally administered D-amphetamine caused a significant decrease in [C-11]raclopride binding at 2 h (13% +/- 5%). Receptor availability was still decreased at 6 h (18% +/- 6%), even though physiological effects had completely returned to baseline. [C-11]Raclopride binding returned to baseline at 24 h. The percentage of [C-11]raclopride displacement was not correlated with plasma D-amphetamine concentrations. In conclusion, orally administered D-amphetamine caused a reliable and prolonged [C-11]raclopride displacement, the magnitude of which is similar to that observed after intravenous administration. Possible mechanisms for the observed prolonged displacement may include persistence of intrasynaptic dopamine and/or receptor internalization. Synapse 51:27-31, 2004. (C) 2003 Wiley-Liss, Inc.