Validity of [123I]?-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity

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. Synapse 46:199–205, 2002.