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Using the Larval Zebrafish Locomotor Asssay in Functional Neurotoxicity Screening: Light Brightness and the Order of Stimulus Presentation Affect the Outcome
Citation:
Jarema, K., D. Hunter, AND S. Padilla. Using the Larval Zebrafish Locomotor Asssay in Functional Neurotoxicity Screening: Light Brightness and the Order of Stimulus Presentation Affect the Outcome. Society of Toxicology (SOT) Annual Meeting, San Diego, CA, March 23 - 27, 2015.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology (SOT) Annual Meeting, March 23-27, 2015, San Diego, CA
Description:
We are evaluating methods to screen/prioritize large numbers of chemicals using 6 day old zebrafish (Danio rerio) as an alternative model for detecting neurotoxic effects. Our behavioral testing paradigm simultaneously tests individual larval zebrafish under sequential light and dark conditions in a 96-well plate. Controlling the duration and intensity of light, we can manipulate activity, assessing changes in locomotion during light-dark transitions, and responses to both light and dark. Manipulating different variables allows us to explore whether the light level affected our ability to detect effects of chemical exposure on locomotor activity. Our testing paradigm employed a wide rangeof light levels (0.01 lux to 51.3 lux) and assessed the activity of larvae dosed acutely with ethanol (a known neurotoxic chemical and disruptor of locomotor activity). The highest ethanol concentration (2%) affected activity regardless of the light level. The lower ethanol concentrations (1% or 0.5%) showed the largest hyperactive effects during the lowest light levels (i.e., dark or at 0.01 lux). At higher light levels (0.5 lux or 51.3 lux), a different pattern emerged showing no difference in activity between control and 0.5% ethanol, and little to no hypoactivity in the 1% group. Moreover, the order of stimulus presentation also affected the outcome: when 0.5 lux followed 0.01 lux, there was no difference in activity among the 1%, 0.5% and control groups, but if that same light level (0.5 lux) followed a much brighter light presentation (51.3 lux), the 1% ethanol group exhibited marked hypoactivity. To sum, the light level and the order of stimuli presentation will affect the sensitivity of the zebrafish larval locomotor assay and the direction of the effect (i.e., either hyper- or hypo-activity). This abstract may not necessarily reflect official Agency policy.