Effects of MDMA and related analogs on plasma 5-HT: relevance to 5-HT transporters in blood and brain.
Samanta Yubero‐lahoz, Mario A Ayestas, Bruce E. Blough, John S. Partilla, Richard B Rothman, Rafael de la Torre, Michael H Baumann
European Journal of Pharmacology January 15, 2012 DOI: 10.1016/j.ejphar.2011.10.033 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study using in vitro and in vivo microdialysis in rats Peer reviewed |
|---|---|
| Population | Rats (blood specimens and brain tissue) |
| Interventions | MDMA MDA |
| Topics | MDMA Serotonin |
| Key findings | MDMA and its metabolite MDA increase plasma serotonin by a SERT-dependent mechanism, with effects ranging from two- to sevenfold above baseline and correlating with SERT substrate potency. In vivo, MDMA caused concurrent increases in extracellular serotonin in blood and brain, but with substantial individual differences. The authors suggest blood serotonin measures may reflect central SERT activity. |
Abstract
(±)-3,4-Methylenedioxymethamphetamine (MDMA) is an illicit drug that evokes transporter-mediated release of serotonin (5-HT) in the brain. 5-HT transporter (SERT) proteins are also expressed in non-neural tissues (e.g., blood), and evidence suggests that MDMA targets platelet SERT to increase plasma 5-HT. Here we tested two hypotheses related to the effects of MDMA on circulating 5-HT. First, to determine if MDMA metabolites might contribute to actions of the drug in vivo, we used in vitro microdialysis in rat blood specimens to examine the effects of MDMA and its metabolites on plasma 5-HT. Second, to determine whether effects of MDMA on plasma 5-HT might be used as an index of central SERT activity, we carried out in vivo microdialysis in blood and brain after intravenous MDMA administration. The in vitro results show that test drugs evoke dose-related increases in plasma 5-HT ranging from two- to sevenfold above baseline, with MDMA and its metabolite, (±)-3,4-methylenedioxyamphetamine (MDA), producing the largest effects. The ability of MDMA and related analogs to elevate plasma 5-HT is correlated with their potency as SERT substrates in rat brain synaptosomes. The in vivo results reveal that MDMA causes concurrent increases in extracellular 5-HT in blood and brain, but there are substantial individual differences in responsiveness to the drug. Collectively, our findings indicate that MDMA and its metabolites increase plasma 5-HT by a SERT-dependent mechanism, and suggest the possibility that measures of evoked 5-HT release in blood may reflect central SERT activity.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- The risk of chronic psychedelic and MDMA microdosing for valvular heart disease Journal of Psychopharmacology August 12, 2023
- Parallel changes in serotonin levels in brain and blood following acute administration of MDMA Journal of Psychopharmacology October 10, 2012
- Human Metabolome Changes after a Single Dose of 3,4-Methylenedioxymethamphetamine (MDMA) with Special Focus on Steroid Metabolism and Inflammation Processes Journal of Proteome Research June 27, 2018
- First Time View on Human Metabolome Changes after a Single Intake of 3,4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects Journal of Proteome Research July 19, 2017
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