Repeated administration of D-amphetamine induces loss of [123I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study.
In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([123I]FP-CIT).


METHODS
Groups of male rats (n = 10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [123I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed.


RESULTS
In d-AMPH but not METH-treated rats, striatal [123I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group.


CONCLUSIONS
These data show that [123I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.
Booij
Jan
J
Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. j.booij@amc.uva.nl
de Bruin
Kora
K
Gunning
W Boudewijn
WB
D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000378:metabolism*
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D008694:Methamphetamine; D000661:Amphetamine