Exploring the impact of MDMA and oxytocin ligands on anxiety and social responses: A comprehensive behavioural and molecular study in the zebrafish model.
Monika Maciag, Olga Doszyn, Artur Wnorowski, Justyna Zmorzyńska, Barbara Budzynska
Journal of Psychopharmacology April 1, 2025 DOI: 10.1177/02698811251324596 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | 3-week-old zebrafish |
| Interventions | MDMA WAY-267 464 L-368 899 |
| Dose | 0.5 μM, 2.5 μM |
| Topics | MDMA Anxiety |
| Keywords | MDMA Ecstasy Neurotransmitters Oxytocin system Interpers Anxiety behaviour Danio rerio Social behaviour Social anxiety Stress response Neuroscience brain chemistry |
| Citations | 4 |
| Key findings | Acute MDMA exposure produces biphasic, dose-dependent anxiolytic and prosocial effects in juvenile zebrafish, mediated partly through the oxytocin system. |
Abstract
Mental disorders, including anxiety and depression, impact nearly 1 billion people worldwide. Recent research has highlighted the potential of certain amphetamine compounds in the therapy of psychiatric disorders, with 3,4-methylenedioxymethamphetamine (MDMA) emerging as a promising candidate. This study investigates the effects of MDMA on anxiety and social behaviours using 3-week-old zebrafish. Additionally, the role of oxytocin in regulating these behaviours was examined through the use of an oxytocin receptor agonist (WAY-267,464) and antagonist (L-368,899). Behavioural effects were assessed using the novel exploration test, light-dark preference test and social preference test. To explore the underlying mechanisms, changes in gene expression in serotonin, oxytocin and vasopressin systems and changes in AKT and EKR1/2 signalling pathways were analysed. Acute MDMA exposure reduced thigmotactic behaviour and increased the social preference index, indicating anxiolytic and prosocial effects. However, these effects were biphasic - the lowest tested dose of 0.5 μM showed anxiogenic and prosocial effects. As the concentration increased, these effects reversed, with a peak at 2.5 μM. MDMA suppressed the expression of serotonin receptors (htr1b and htr2b) and transporter (scl6a4) genes while increasing oxytocin receptors (oxtra and oxtrb) genes, decreasing vasopressin receptor (avpr1aa) gene expression, and reducing AKT phosphorylation. The oxytocin receptor agonist mimicked MDMA's effects, while the antagonist had no significant effect on anxiety or social behaviour. MDMA demonstrates therapeutic potential for treating anxiety disorders and social impairments. Moreover, 3-week-old zebrafish proved to be a valuable model for neurobehavioural research and high-throughput screening of psychiatric treatments.
Comparable studies
Other preclinical and animal studies on MDMA for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Mice | 2015 | Preclinical experimental study | |
| Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice Adolescent (postnatal day 29-40) and adult (postnatal day 50-61) male mice | 2014 | Experimental study | |
| MDMA in Adolescent Male Rats Adolescent male rats (postnatal day 45) | 2006 | Controlled experiment | n = 12 |
| Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Rodents | 2024 | Review | |
| Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice 2-month-old Balb/c male mice (25-35 g) | 2013 | Observational study | n = 70 |
Citations in the library
Cites 25
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology 2013
- Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration Social Neuroscience June 25, 2009
and 20 more in the library