Locomotion and Behavioral Toxicity in Larval Zebrafish: Background, Methods, and Data - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 155

the two lowest concentrations of valproate were without effect, while the highest
concentration (33 M) produced robust increases in locomotion in the dark periods

only. These results are similar to those reported for the effects of developmental
exposure to valproate in mammals, where behavioral alterations were seen in the
offspring of both humans and experimental animals (e.g., Vorhees, 1987; Moore
et al., 2000). It is interesting to note that hyperactivity is reported for children of
mothers taking anticonvulsants (including valproate) during gestation. These data are
encouraging as they indicate that the larval zebrafish behavioral assay can detect
abnormal behavioral effects at exposure levels below those that produce frank
teratogenic effects.

m

12.7 CONCLUSIONS

12.7.1 Summary

The increasing use of larval zebrafish in toxicology, pharmacology, and biology
emphasizes the need for a firm understanding of their behavior and the variables that
influence it. Behavior is unique in that it represents the interface between the
internal environment of an organism and the external environment in which the
organism lives. From a practical view, therefore, care must be taken in research to
identify and control the environmental variables that influence behavior. Stringent
control over the testing environment will enhance reproducibility of results. In
addition, systematic manipulation of environmental variables can lead to a fuller
account of the effects on behavior of chemical treatments, whether environmental
pollutants or drugs, and improve our understanding of the specificity of chemical
effects on behavior. The behavioral preparation described in this chapter is versatile
in allowing repeated manipulation of key variables such as lighting condition and
duration, which can affect the response of larval zebrafish to chemical exposures.
It is, however, reasonable to assume that we have only begun to exploit the
preparation.

12.7.2 Future Avenues

Further studies are needed on the influence of light intensity on behavior, and its
interaction with toxicant effects. The visual systemof fish, including larvae, is highly
developed and intimately related to behavior and survival. It is conceivable that
visual thresholdsmay be obtainedwith suitablemodification of the testing paradigm.
Still other studies could investigate the habituation of behavior. Habituation is a
primitive form of learning that appears to be virtually universal throughout the
animal kingdom. Considerable information is currently available on the variables
that influence habituation, including many drugs, and on its neurobiological sub-
strates. It is likely that tests of habituation in toxicant-exposed zebrafish will increase
in the coming years.