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

Research output: Contribution to journalArticle

Abstract

Recent [123I]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, [123I]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 [123I]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 [123I]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 [123I]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 [123I]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 [123I]β-CIT can detect changes in SERT density secondary to MDMA-induced neurotoxicity in the hypothalamic/midbrain region, and possibly other brain regions.

Original languageEnglish (US)
Pages (from-to)199-205
Number of pages7
JournalSynapse
Volume46
Issue number3
DOIs
StatePublished - Dec 1 2002

Keywords

  • 5-HT
  • MDMA
  • Neurotoxicity
  • Validity
  • [I]β-CIT SPECT

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Reneman, L., Booij, J., Habraken, J. B. A., De Bruin, K., Hatzidimitriou, G., Den Heeten, G. J., & Ricaurte, G. A. (2002). Validity of [123I]β-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity. Synapse, 46(3), 199-205. https://doi.org/10.1002/syn.10130