DOPAMINE TRANSPORTER BINDING POTENTIAL INCREASES WITH AN ACUTE DOSE OF MDMA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. AIMS: MDMA methylene-dioxymethamphetamine or ecstasy is a widely abused psychoactive drug, considered to produce its empathic effects primarily by modulating serotonin transporter SERT function and brain serotonin activity. MDMA is also a mild psychomotor stimulant in humans and nonhuman primates, an effect reportedly mediated by dopaminergic activity. We previously demonstrated that MDMA is an effective substrate for the dopamine DAT transporter. Based on these findings, we hypothesized that an acute dose of MDMA would occupy the DAT in vivo, as manifest by reduced DAT binding potential. METHODS: In rhesus monkeys n=5, we used PET imaging and the DAT ligand (11C)CFT to measure DAT binding potential. PET imaging was performed over 60 min, with regions of interest drawn over striatum and cerebellum and binding potential calculated using the SSRT method. Following generation of baseline DAT binding potential, MDMA (1.5 mg/kg was injected intravenously and imaging was repeated 1 hour after drug injection. RESULTS: Contrary to expectations, DAT binding potential measured with (11C)CFT was consistently higher, 121 percent (n=5, than baseline values, following an acute dose of MDMA. Intramuscular MDMA and the DAT ligand (11C)altropane yielded inconsistent changes, confirming our previous findings that METH effects are sensitive to route of administration and time. CONCLUSIONS: These unanticipated findings are conceivably attributable to neurochemical properties of METH or technical reasons. MDMA may alter DAT regulatory mechanisms acutely to increase DAT availability or alternately, MDMA blockade of striatal SERT could prevent SERT occupancy by (11C)CFT to increase PET ligand availability for the DAT.