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

Parenterally administered D ‐amphetamine has been used as a challenge drug to release dopamine, which in turns inhibits [ 11 C]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 [ 11 C]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 [ 11 C]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. [ 11 C]Raclopride binding returned to baseline at 24 h. The percentage of [ 11 C]raclopride displacement was not correlated with plasma D ‐amphetamine concentrations. In conclusion, orally administered D ‐amphetamine caused a reliable and prolonged [ 11 C]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. © 2003 Wiley‐Liss, Inc.