Evaluation of the enantioselective neurotoxicity of MDPV in zebrafish larvae

Background: The rising recreational use of synthetic cathinones (SC), especially among youth [1], has led to their detection in aquatic environments at ng–μg L‒1 levels [2], posing potential risks to freshwater vertebrates [3]. As SC are designed to act on the nervous system, their presence in the environment may cause unpredictable adverse effects in non-target organisms [1]. Among these compounds, 3,4-methylenedioxypyrovalerone (MDPV) has been identified in wastewater and aquatic systems [2], but its enantioselective ecotoxicological effects remain poorly understood. Objective: This work aimed to evaluate the behavioral effects of racemic MDPV ((R,S)) and its enantiomers ((R) and (S)) in early life stages of zebrafish (Danio rerio). Methods: Embryos (≈ 3-hours post-fertilization (hpf)) were exposed to MDPV forms (0.18−2.8 μg L‒1) for 96-h at 28 °C, using 50 animals per concentration and control group (5 replicates). Larvae behavior was assessed at 120-hpf in a random subsample of 5 individuals per concentration and replicate, evaluating locomotion and avoidance responses. Results: (R,S)-MDPV mainly induced hyperlocomotion, increasing speed and activity, along with reduced center exploration. (R)-MDPV produced hypoactivity, whereas (S)-MDPV caused pronounced locomotor suppression, altered spatial exploration, and impaired avoidance behavior. Clear enantioselective differences were observed, with (S)-MDPV emerging as the most neurotoxic, while the racemate generally showed lower toxicity than the individual enantiomers. Conclusions: MDPV disrupts zebrafish larval neurobehavior in a concentration-dependent and enantioselective manner, with (S)-MDPV being the most toxic. These findings underscore the importance of considering chirality in environmental risk assessments of psychoactive contaminants, as behavioral alterations can compromise survival by reducing predator avoidance.