Developmental exposure to MDMA (ecstasy) in zebrafish embryos reproduces the neurotoxicity adverse outcome ‘lower motor activity’ described in humans

The recreational use of MDMA (ecstasy) by pregnant women is associated with impaired neuromotor function in infants, but the Adverse Outcome Pathway behind this effect is not clear yet. We present for the first time the evaluation of developmental neurotoxic (DNT) effects of MDMA in zebrafish embryos. The aim of the study was to determine whether the zebrafish model reproduces the adverse outcome occurring in humans. We have studied the DNT effects of MDMA in zebrafish within a range of 5–250 μM performing different behavioural tests: spontaneous tail-coiling and light-dark locomotor response; after exposing the embryos to 4 different scenarios combining changes in pH, in starting exposure time and exposure duration. In these scenarios we evaluated the effects of MDMA in general embryonic development and compared the concentrations producing them with those inducing specific DNT effects. As a result, we have established the experimental conditions leading to the adverse outcome “lower motor activity” in zebrafish without producing general developmental delay or general toxicity. The experimental condition chosen opens the door to use this model in future mechanistic investigations to better characterize the Adverse Outcome Pathway associated with the adverse effects caused by MDMA prenatal exposure in humans.