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 [11C]raclopride binding to dopaminergic D2 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 [11C]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 [11C]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. [11C]Raclopride binding returned to baseline at 24 h. The percentage of [11C]raclopride displacement was not correlated with plasma D-amphetamine concentrations. In conclusion, orally administered D-amphetamine caused a reliable and prolonged [11C]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.
Cárdenas
Laura
L
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Houle
Sylvain
S
Kapur
Shitij
S
Busto
Usoa E
UE
D000284:Administration, Oral; D000328:Adult; D002250:Carbon Radioisotopes / Q000378:metabolism; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology; D020891:Raclopride / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods*
D002250:Carbon Radioisotopes; D020891:Raclopride; D003913:Dextroamphetamine