Drug consumption-based epidemiology to evaluate the impact of selected pharmaceuticals dispersed in wastewater on the nervous system in Zebrafish

Danio rerio (zebrafish) has become an increasingly important model for assessing the neurotoxic and ecological impacts of anthropogenic pollutants. Through investigations of pesticides, antibiotics, psychoactive pharmaceuticals, and complex environmental mixtures, these studies collectively demonstrate that environmentally relevant concentrations of pharmaceutical compounds, although at sublethal or subtherapeutic levels, can significantly affect behavior, neural integrity, and physiology. Rotenone and deltamethrin pesticide exposures disrupted dopaminergic pathways and induced neuronal apoptosis, mirroring Parkinsonian-like pathologies and underscoring conserved vulnerabilities across vertebrates. Prolonged exposure to the antibiotic amoxicillin/clavulanic acid altered locomotor activity, stress responses, social behavior, and neurotransmitter-related gene expression, revealing that antibiotics are not ecologically inert once released into aquatic environments from wastewater treatment plants. Similarly, diazepam exposure elicited sex-dependent behavioral and molecular effects consistent with GABAergic modulation, further emphasizing the ecological relevance of pharmaceutical pollutants. Complementary studies using river water from the Milan area confirmed that complex pollutant mixtures can induce behavioral disinhibition and physiological stress, underscoring the limitations of single-compound toxicology. Collectively, these findings position the zebrafish as an integrative model that links behavioral, molecular, and ecological endpoints in environmental neurotoxicology. The results call for more comprehensive risk assessments that incorporate chronic, low-level, and mixture-based exposures. Strengthening environmental regulations and wastewater management is essential to mitigate the widespread and often underestimated impacts of chemical pollution on aquatic ecosystems and human health.