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Exploring the impact of MDMA and oxytocin ligands on anxiety and social responses: A comprehensive behavioural and molecular study in the zebrafish model.

Journal of psychopharmacology (Oxford, England)
April 1, 2025
Monika Maciag et al. (5 authors)
Journal ArticleAnimal Study
Study Details

Study Goal

The researchers aimed to determine the effects of MDMA on anxiety and social behaviors in zebrafish, and to explore the role of oxytocin in regulating these behaviors.

Results Summary

Acute MDMA exposure reduced anxiety-like behavior and increased social preference in zebrafish, with effects varying by dose. The lowest dose (0.5 μM) had anxiogenic effects, while higher doses (peaking at 2.5 μM) showed anxiolytic and prosocial effects. MDMA altered gene expression in serotonin, oxytocin, and vasopressin systems, and reduced AKT phosphorylation.

Population

3-week-old zebrafish

Effective Dosage

0.5 μM to 2.5 μM (acute exposure)

Duration

Acute (single exposure)

Interactions

None mentioned

Extracted Claims (10)
InterventionDirectionEndpointPopulationDosageImpactClaim #
Acute MDMA exposure
decrease
thigmotactic behaviour
3-week-old zebrafish
-
reduced
#1
Acute MDMA exposure
increase
social preference index
3-week-old zebrafish
-
increased
#2
MDMA (lowest tested dose of 0.5 μM)
increase
anxiety and social behaviours
3-week-old zebrafish
0.5 μM
showed anxiogenic and prosocial effects
#3
MDMA (concentration increased)
increase
anxiolytic and prosocial effects
3-week-old zebrafish
2.5 μM
effects reversed, with a peak at 2.5 μM
#4
MDMA
decrease
serotonin receptors (htr1b and htr2b) and transporter (scl6a4) genes
3-week-old zebrafish
-
suppressed the expression
#5
MDMA
increase
oxytocin receptors (oxtra and oxtrb) genes
3-week-old zebrafish
-
increasing
#6
MDMA
decrease
vasopressin receptor (avpr1aa) gene expression
3-week-old zebrafish
-
decreasing
#7
MDMA
decrease
AKT phosphorylation
3-week-old zebrafish
-
reducing
#8
oxytocin receptor agonist (WAY-267,464)
increase
anxiety and social behaviour
3-week-old zebrafish
-
mimicked MDMA's effects
#9
oxytocin receptor antagonist (L-368,899)
no change
anxiety or social behaviour
3-week-old zebrafish
-
had no significant effect
#10
Abstract

BACKGROUND: 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. AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Medical Subject Headings (MeSH)
AnimalsZebrafishN-Methyl-3,4-methylenedioxyamphetamineOxytocinSocial BehaviorAnxietyReceptors, OxytocinBehavior, AnimalDisease Models, AnimalMaleLigandsSignal TransductionFemaleCamphanesPiperazines
Study Links
Quality Scores
SafetyNot Assessed
Efficacy70/10
Quality80/10
Research Impact Scores
APT Score0.05
Weight Score1.95
Normalized Score0.64
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