Validity of [123I]beta-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity.
Recent [123I]beta-CIT single-photon emission computed tomography (SPECT) studies revealed decreased serotonin transporters (SERT) density in the brain of humans with a history of MDMA ("Ecstasy") use. However, [123I]beta-CIT SPECT has until now not been validated as a method for detecting such serotonergic lesions. Therefore, the present study was undertaken. Following baseline [123I]beta-CIT SPECT scans, a rhesus monkey was treated with MDMA (5 mg/kg, s.c. twice daily for 4 consecutive days). SPECT studies 4, 10, and 31 days after MDMA treatment revealed decreases in [123I]beta-CIT binding ratios in the SERT-rich brain region studied (hypothalamic/midbrain region), with SERT density reduced by 39% in this brain region 31 days after treatment. Data obtained with SPECT studies correlated well with SERT density determined with autoradiography after sacrifice of the animal (-34%). In addition, ex vivo [123I]beta-CIT binding studies in rats 1 week after treatment with neurotoxic doses of MDMA (20 mg/kg s.c. twice daily for 4 consecutive days) revealed significant reductions in [123I]beta-CIT binding in SERT-rich regions (including the hypothalamus) when compared to saline-treated rats. The combined results of these studies indicate that SPECT imaging of SERT with [123I]beta-CIT can detect changes in SERT density secondary to MDMA-induced neurotoxicity in the hypothalamic/midbrain region, and possibly other brain regions.
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging / Q000379:methods; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000378:metabolism / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D018490:Serotonin Agents / Q000378:metabolism / Q000633:toxicity*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D007457:Iodine Radioisotopes; D018490:Serotonin Agents; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine