Locomotion and Behavioral Toxicity in Larval Zebrafish: Background, Methods, and Data - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 154

control. Brief dips in activity at the beginning of the light periods, however, suggested
some slight residual in visual competence (see Matsui et al., 2006, for ethanol effects
on visual thresholds in larval zebrafish).
The results of these studies indicate the remarkable versatility of the behavioral
testing paradigm. The effects of several variables on larval locomotion have been
briefly summarized. There are more variables, for example, variations in lighting
intensity and duration, that will further enrich our understanding of larval locomotion
and its determinants.
The ultimate goal of these studies, to reiterate, was to establish a testing
procedure for rapidly evaluating developmental exposures to neurotoxic chemicals.
To this end, data are presented next for valproate, an anticonvulsant that is toxic to
the developing nervous system in mammals, including humans (Bescoby-Chambers
et al., 2001; Alsdorf andWyszynski, 2005; Genton et al., 2006;Magalhaes et al., 2007;
Yochum et al., 2008). Larvae were exposed to varying concentrations of valproate
from day 1 through day 5 post fertilization. Following one day of washout, the larvae
were tested under alternating 10 min periods of light and dark. The results of this study
are shown in Fig. 12.5. Results are presented only for larvae that appeared structurally
normal; all abnormal embryos were eliminated from the analyses. In particular, larvae
receiving 100 M valproate showed prominent signs of structural abnormalities

and developmental delay, and were therefore not included. Figure 12.5 shows that

m

Figure 12.5 Effects of developmental exposure to valproate on locomotor activity. Larvae (n¼13 - 28)
were exposed to Hanks' buffer solution (control) or a dose of valproate from 8 h post fertilization to 5 days
post fertilization. Activity testing occurred on day 6 post fertilization. Each symbol represents meanSEM
distancemoved in 2min. Lighting conditions alternated, with 10min of light followed by 10min of dark for
three cycles (denoted by the bar in the lower portion of the figure). Valproate noticeably increased activity in
larvae that had been exposed to 33 m M during development. Hyperactivity was, however, obtained only in

the dark periods.