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Abstract

The zebrafish embryo as an alternative complex vertebrate model can be utilized as a valuable tool for assessing developmental neurotoxicity. Analysis of embryonic behavior in particular can be used to detect even subtle changes that may later have serious effects on the fitness of the organism. However, since behavior is a sensitive endpoint, it can be influenced by various confounding factors. I implemented a generalized additive modeling (GAM) approach to account for natural variability of the fish and discriminate treatment-related alterations in the tail coiling behavior from several cofounding factors. To complement this analysis, I inspected the integrity of secondary motoneurons and skeletal muscle using antibody staining and birefringence microscopy, respectively. The impairments of both structural endpoints align with the behavior outcomes. After successful proof-of-concept, I used the GAM approach to investigate a suspected metabolite of the insecticide imidacloprid, desnitro-imidacloprid. Here, I could not detect a significant alteration compared to the control. At least for zebrafish, I conclude that desnitro-imidacloprid does not show a comparable developmental neurotoxic potential like nicotine. Finally, I investigated the impacts of the antidepressants sertraline, paroxetine and venlafaxine on the zebrafish embryo. Shared effects of all three compounds in the FET test included cardiotoxicity, degeneration of the fin seam and a loss of equilibrioception. Experiments on sublethal developmental neurotoxic effects on embryonic behavior showed altered movement patterns and lower visual-motor response to a light stressor in a concentration dependent manner for all substances. I concluded that antidepressants could lower the fish embryos´ fitness by impacting heart health and equilibrium while swimming. In the case of sertraline, embryonic behavioral alterations have been visible at environmentally relevant concentrations and thus it can pose a realistic threat to fish in the aquatic environment. Behavior as an endpoint, and in particular the coiling movements, has been shown to be the most sensitive to detect potential developmental neurotoxicity.