Degree of [123I]-Beta-CIT binding in a rhesus monkey and rats after neurotoxic MDMA regimen was used in a study of the validity of Beta-CIT as a measure of serotonin transporter density in vivo. SPECT scans were performed twice before and 3 times after a rhesus monkey was given 2 doses of 5 mg/kg MDMA daily for 4 consecutive days, with post-drug scans performed 4, 10 and 31 days after MDMA treatment. Scans from MDMA-treated monkeys were compared with scans in control animals. Monkeys receiving SPECT scans were given 222 MBq radiolabeled Beta-CIT. Because electrodes had previously been implanted in the MDMA-treated monkey, Beta-CIT binding was not examined in the cortex. Region of analysis methods were used to assess level of Beta-CIT binding (presumed to be measuring SERT density. Hypothalamus/midbrain Beta-CIT binding was compared with cerebellar and striatal binding, with cerebellum assumed to be free of SERT. Both monkeys were killed 3 wks after the last SPECT scan, and autoradiography was performed on brains with radiolabeled citalopram. Rats given 2 daily doses of saline or 20 mg/kg MDMA for 4 days were injected with 1.85 MBq Beta-CIT 7 days post-treatment. Rats were killed 3 h later, and brain region radioactivity was directly measured in cortical areas, hippocampus, striatum, thalamus, raphe, and midbrain. SPECT scans in the MDMA-treated monkey found reduced Beta-CIT binding after MDMA treatment compared to baseline scans, with binding values lowest 4 days after treatment, and binding values 31 days after treatment higher than on 4 or 10 days post-drug. At 10 days post-drug, binding was reduced by 39% of amounts measured pre-drug, but at Day 31, SERT values were only reduced by 34% of pre-drug binding. Striatal Beta-CIT binding ratios were reduced by 13% 10 days post-drug and 26% 31 days post-drug, potentially indicating increased reduction. Beta-CIT binding compared well with autoradiographic pictures of serotonin transporter sites. Beta-CIT binding in MDMA-treated rats was lower in areas of the brain with serotonin neurons and unaffected in areas with many dopamine neurons. Degree of reduced Beta-CIT binding covaried with number of serotonin neurons present in a given brain region. Study findings suggest that Beta-CIT can serve as an adequate means of assessing serotonin transporter density in vivo, and that it may detect changes in serotonin transporter site availability (internalization) and damage to serotonin axons after MDMA. It is interesting to note reduction in apparent SERT sites declined 31 days after 4 days of twice-daily dosing with MDMA, suggesting either that there are non-neurotoxic brain changes that result in lower serotonin transporter sites or not all reduction in SERT density is due to irreversible processes. This is also another study reporting some reduced striatal DA function in a monkey after a repeated-dose MDMA regimen, with reduction in DA site density somewhat greater 31 days after treatment. However, unlike the findings of Ricaurte et al (2002), striatal Beta-CIT binding is minimal. Considering that the same research team failed to find reduced striatal dopamine transporter uptake sites in ecstasy users with the same ligand (Beta-CIT), it would appear that humans and some non-human primates experience different long-term effects after MDMA.