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Neurovascular Uncoupling: Multimodal Imaging Delineates the Acute Effects of MDMA

Tudor M. Ionescu, Mario Amend, Tadashi Watabe, Jun Hatazawa, Andreas Maurer, Gerald Reischl, Bernd J. Pichler, Hans F. Wehrl, Kristina Herfert

bioRxiv Preprint Server February 14, 2022 preprint DOI: 10.1101/2022.02.14.480365 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical study
Population Rats
Intervention MDMA
Topics MDMA
Citations 1
Key points MDMA leads to inhibition of brain activity in fMRI studies, contradicting earlier hypotheses of mainly excitatory effects.

Abstract

Psychedelic compounds have attracted increasing interest in recent years due to their therapeutic potential for psychiatric disorders. Methylenedioxymethamphetamine (MDMA) is currently being investigated in clinical trials to treat post-traumatic stress disorder. To understand the acute effects of psychedelic drugs in vivo, functional MR imaging (fMRI) has been widely used in recent years. Notably, fMRI studies have shown that MDMA leads to inhibition of brain activity, challenging earlier hypotheses indicating mainly excitatory effects. However, interpretation of hemodynamic changes induced by psychedelics is challenging because of the potent vascular effects associated with this class of substances. Therefore, this study aimed to investigate the acute effects of MDMA using simultaneous positron emission tomography (PET)/fMRI in rats. For this purpose, hemodynamic changes measured by BOLD-fMRI were related to alterations in glucose utilization and serotonin transporter (SERT) occupancy, investigated using [18F]FDG functional PET (fPET) and [11C]DASB PET.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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