Parallel changes in serotonin levels in brain and blood following acute administration of MDMA

In rats, MDMA (20 mg/kg) caused a parallel drop in serotonin levels in the frontal cortex and blood, with decreases of 63% and 46% respectively at 2 hours, partial recovery by 8 hours (42% and 38% below control), and further recovery by 18 hours (19% and 24% below control). A tryptophan supplement (82.5 mg/kg) raised serotonin in both brain (39%) and blood (26%) in naïve rats, but after MDMA, the same supplement raised brain serotonin only 26% and had no effect on blood serotonin. Blood serotonin appears to be a useful marker for brain serotonin levels after acute MDMA, suggesting platelet serotonin could serve similarly in human studies.

Study at a glance

Abstract

Recent studies have demonstrated a similar acute effect of 3,4- methylenedioxymethamphetamine (MDMA) in blood platelets and brain tissue via action on the serotonin transporter. To investigate the validity of blood serotonin as a peripheral marker for central serotonin in this regard, we administered MDMA (20 mg/kg i.p.) to rats and observed a parallel decrease in serotonin levels in the frontal cortex and blood at 2 h (63% and 46% respectively) with some recovery evident at 8 h (42% and 38%) and more so at 18 h (19% and 24% below control levels). Administration of a tryptophan supplement (82.5 mg/kg p.o.) to naïve rats produced parallel increases in serotonin levels 2 h later in the frontal cortex (39%) and blood (26%). Following MDMA administration, the same dose of tryptophan caused a smaller (26%) rise in brain serotonin whereas in blood it had no effect. We conclude that blood serotonin is a useful marker for brain serotonin levels in the rat following acute administration of MDMA and this finding highlights the possible use of platelet serotonin as a marker for brain serotonin in human studies involving MDMA.