Locomotor effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in mice: psychostimulant effects, stereotypy, and sensitization
Michael D. Berquist, Sebastian Leth-Petersen, Jesper L. Kristensen, William E Fantegrossi
Psychopharmacology November 15, 2019 DOI: 10.1007/s00213-019-05380-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study (preclinical) Peer reviewed |
|---|---|
| Population | Male mice |
| Interventions | MDMA methamphetamine |
| Topics | MDMA |
| Key findings | d2-MDMA was less effective than MDMA at eliciting horizontal locomotion in male mice, but the difference diminished as cumulative administrations increased. Both drugs produced sensitized locomotor responses that cross-sensitized to methamphetamine, and d2-MDMA may be less susceptible to inducing sensitization to stereotyped movements depending on the dosing regimen. |
Abstract
There is a renewed interest in the use of 3,4-methylenedioxymethamphetamine (MDMA) for treating psychiatric conditions. Although MDMA has entered phase II clinical trials and shows promise as an adjunct treatment, there is an extensive literature detailing the potential neurotoxicity and adverse neurobehavioral effects associated with MDMA use. Previous research indicates that the adverse effects of MDMA may be due to its metabolism into reactive catechols that can enter the brain and serve directly as neurotoxicants. One approach to mitigate MDMA’s potential for adverse effects is to reduce O-demethylation by deuterating the methylenedioxy ring of MDMA. There are no studies that have evaluated the effects of deuterating MDMA on behavioral outcomes. The purpose of the present study was to assess the motor-stimulant effects of deuterated MDMA (d2-MDMA) and compare them to MDMA in male mice. Two experiments were performed to quantify mouse locomotor activity and to vary the drug administration regimen (single bolus administration or cumulative administration). The results of Experiments 1 and 2 indicate that d2-MDMA is less effective at eliciting horizontal locomotion than MDMA; however, the differences between the compounds diminish as the number of cumulative administrations increase. Both d2-MDMA and MDMA can elicit sensitized responses, and these effects cross-sensitize to the prototypical drug of abuse methamphetamine. Thus, d2-MDMA functions as a locomotor stimulant similar to MDMA, but, depending on the dosing regimen, may be less susceptible to inducing sensitization to stereotyped movements. These findings indicate that d2-MDMA is behaviorally active and produces locomotor effects that are similar to MDMA, which warrant additional assessments of d2-MDMA’s behavioral and physiological effects to determine the conditions under which this compound may serve as a relatively safer alternative to MDMA for clinical use.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- MDMA treatment paired with a trauma-cue promotes adaptive stress responses in a translational model of PTSD in rats Translational Psychiatry May 3, 2022
- MDMA as an early post-trauma intervention in a translational animal model of PTSD. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 24, 2026
- Effects of ambient temperature on locomotor activity and place conditioning elicited by abused psychostimulants in mice: Role of 3,4-methylenedioxy moiety. Drug and Alcohol Dependence September 1, 2023
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