Photomotor response data analysis approach to assess chemical neurotoxicity with the zebrafish embryo.

The photomotor response (PMR) of zebrafish embryos, a light pulse-triggered undirected movement, is known to be altered by neuroactive chemicals.  Here, we developed an approach for data analysis of the distribution of PMR movement activities along the time axis; differences between treatment and respective controls are expressed by an aggregated value integrating the time-resolved density of the movement parameter as a measure for a chemically elicited PMR effect. Logistic concentration-PMR effect relationships were modeled for neuroactive test compounds with different modes of action (acetylcholinesterase inhibition, activation and inhibition of voltage-gated sodium channels); 50% effect concentrations (EC50) were in the low to medium µM range (EC50 10 µM for tricaine). Modulation of movement activities in different phases of the PMR (i.e., "fingerprint") by neuroactive test compounds varied across concentrations showing that mode of action-specific PMR fingerprints are also concentration-dependent. Above 10% lethal concentrations causing 10% lethality (LC10; 48h) 3,4-dichloroaniline caused movement inhibition. This substance presumably is not neuroactive, its effect on the PMR therefore was considered as a secondary toxic effect. Quantitative morphological examinations of chemically exposed embryos showed that malformations occurred only above PMR effect concentrations, indicating that changes in the PMR were not due to such indirect effects. The PMR assay will provide useful measures in ecotoxicological risk assessment of neuroactive chemicals with zebrafish embryos and could potentially be used to infer acute fish toxicity levels from PMR effect concentrations of neurotoxic compounds.