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Validity of [123I]β‐CIT SPECT in detecting MDMA‐induced serotonergic neurotoxicity

Liesbeth Reneman, Jan Booij, Jan B. A. Habraken, Kora de Bruin, George Hatzidimitriou, Gerard J. den Heeten, George A. Ricaurte

Synapse September 5, 2002 DOI: 10.1002/syn.10130 via OpenAlex

Summary

AI-generated from the abstract

SPECT imaging with [123I]β-CIT can detect reductions in serotonin transporter density caused by MDMA neurotoxicity. A rhesus monkey treated with MDMA showed a 39% decrease in SERT binding in the hypothalamic/midbrain region 31 days after treatment, matching autoradiography data (−34%). Rat studies confirmed significant binding reductions in SERT-rich regions one week after neurotoxic MDMA doses. The findings validate [123I]β-CIT SPECT as a method for measuring MDMA-induced serotonergic damage in the brain.

Study at a glance

Characteristics Preclinical experimental study Peer reviewed
Sample size 1
Population Rhesus monkey and rats
Intervention MDMA
Dose 5 mg/kg s.c. twice daily for 4 consecutive days
Duration 31 days post-treatment
Topics MDMA Serotonin
Keywords Binding potential Neurotoxicity Serotonin transporter
Citations 33
Key finding SPECT imaging with [123I]β-CIT can detect MDMA-induced reductions in serotonin transporter density in the hypothalamic/midbrain region.

Abstract

Abstract Recent [ 123 I]β‐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, [ 123 I]β‐CIT SPECT has until now not been validated as a method for detecting such serotonergic lesions. Therefore, the present study was undertaken. Following baseline [ 123 I]β‐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 [ 123 I]β‐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 [ 123 I]β‐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 [ 123 I]β‐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 [ 123 I]β‐CIT can detect changes in SERT density secondary to MDMA‐induced neurotoxicity in the hypothalamic/midbrain region, and possibly other brain regions. Synapse 46:199–205, 2002. © 2002 Wiley‐Liss, Inc.

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