Dopamine transporter binding potential increases following an acute dose of MDMA (Ecstasy)

Objectives MDMA (methylene-dioxymethamphetamine or ecstasy) is a widely used psychoactive drug, considered to act primarily via modulating serotonin transporter (SERT) function. We previously demonstrated that MDMA is also a substrate for the dopamine (DAT) and norepinephrine transporter (Verrico et al, 2007). A number of studies have investigated the effects of chronic (repeated) MDMA exposure on the SERT and DAT. Presently, we investigated whether MDMA alters DAT binding potential(BP) after a single acute dose.

Methods In rhesus monkeys (n=5), we used PET imaging and the DAT ligands ¹¹C-CFT or ¹¹C-Altropane to measure DAT BP. PET imaging was performed a over 60 min (Eight 15 sec frames and 1.0 min frames thereafter) using a GE PC4096 PET camera. ROI’s were drawn over striatum and cerebellum and binding potential was calculated using the SRTM method. Following genaration of base line images, MDMA (1.5 mg/kg) was injected intravenously and imaging was repeated 1 hour after drug injection.

Results DAT BP measured with ¹¹C-CFT consistently increased 121% (n=5). Intramuscular MDMA and the DAT ligand ¹¹C-Altropane yielded inconsistent changes, indicating that the observations with ¹¹C-CFT are route and time-sensitive.

Conclusions The findings with ¹¹C-CFT and MDMA are contrary to the expectations, that MDMA would either have minimal effect or reduce DAT occupancy by ¹¹C-CFT. It is possible that MDMA inhibition of striatal SERT blocks SERT binding by ¹¹C-CFT to increase PET ligand availability for the DAT. Alternately, MDMA may alter DAT regulatory mechanisms acutely to increase DAT availability.

Research Support Grant support: DA11558; DA06303; DA 15305; RR00168