Changes in serotonin transporter (5-HTT) gene expression in peripheral blood cells after MDMA intake.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is an amphetamine derivative abused worldwide. Although data report that relatively high doses of MDMA deplete serotonin (5-HT) content and decrease the availability of serotonin transporters (5-HTT), there is no available evidence as to the adaptive mechanisms taking place in 5-HTT gene expression following MDMA intake in humans. To evaluate the pharmacological effects of MDMA on 5-HTT gene expression, using peripheral mononuclear cells as a biomarker of the central nervous system, and study whether an association exists between 5-HTT gene expression and psychobiological scores. A randomized, double-blind, controlled trial was conducted in 18 (nine women) healthy recreational MDMA users. Subjects were genotyped for 5-HTT linked polymorphism region (5-HTTLPR). MDMA 75mg or placebo was administered; Profile of Mood States (POMS) and 5-HTT gene expression measures were performed at baseline, 90, and 165min post administration. POMS scores were correlated with changes in gene expression. The administration of 75mg MDMA induced a significant twofold increase in 5-HTT gene expression after 165min of drug administration. Significant associations were found between gene expression and POMS scores after MDMA administration. Results for each gender and 5-HTTLPR genotype are also reported. Preliminary results show that MDMA causes substantial regulatory changes in the expression of serotonergic markers, likely being modulated by the 5-HTTLPR polymorphism. Changes in 5-HTT gene expression may play an important role in the regulation of mood state.