Validity of in vivo [123I]beta-CIT SPECT in detecting MDMA-induced neurotoxicity in rats.
This study investigated the ability of a high-resolution pinhole single-photon emission computed tomography (SPECT) system, with [(123)I]beta-CIT as a radiotracer, to detect 3,4-methelenedioxymethamphetamine (MDMA, 'Ecstasy')-induced loss of serotonin transporters (SERTs) in the living rat brain. In vivo striatal and thalamic [(123)I]beta-CIT binding ratios, representing specific binding to dopamine and serotonin transporters, respectively, were determined 7 days before as well as 10 days after treatment of rats with neurotoxic doses of MDMA using SPECT. At the end of the experiment, radioactivity ratios were also determined ex vivo, and compared to control data. Both in vivo and ex vivo, thalamic, but not striatal, uptake ratios were statistical significantly reduced after MDMA treatment. These data show that [(123)I]beta-CIT SPECT may be able to detect MDMA-induced loss of SERTs. Therefore, this may be a promising technique to perform serial studies on MDMA-induced serotonergic neurotoxicity in living small animals.
de Win
Maartje M L
MM
Department of Radiology, University of Amsterdam, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.m.dewin@amc.uva.nl
de Jeu
Rogier A M
RA
de Bruin
Kora
K
Habraken
Jan B A
JB
Reneman
Liesbeth
L
Booij
Jan
J
den Heeten
Gerard J
GJ
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D002352:Carrier Proteins; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006213:Hallucinogens / Q000633:toxicity; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D002352:Carrier Proteins; D006213:Hallucinogens; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine