PERSISTENT EFFECTS OF EMBRYONIC EXPOSURE TO PROCONVULSANT OR ANITCONVULSANT COMPOUNDS IN ZEBRAFISH, Danio rerio.

KL Law, KC Brannen

Charles River Laboratories, Horsham, PA

Anticonvulsant medications are often prescribed to women during pregnancy; however, some of these drugs may have the potential to cause developmental toxicity. In addition, there is growing concern that exposures to pharmaceuticals or chemicals in utero may have persistent effects on health that are not obvious at the time of birth (the hypothesis of the fetal basis of adult disease). With a transparent vertebrate model, the zebrafish, organ growth and development can be monitored while embryos are exposed to known test agents. We hypothesized that a proconvulsant and anticonvulsant compound exposures during embryonic development would cause persistent changes in susceptibility to the proconvulsant agent pentylenetetrazole (PTZ)-induced seizures during the larval period. Zebrafish embryos were exposed to sub-teratogenic concentrations of several pro- or anticonvulsant compounds from approximately 6 to 50 hour post-fertilization. At 6 days post-fertilization (dpf), seizures and were induced in these larvae by treatment with PTZ to determine if embryonic exposures affected the PTZ response during the larval stage. While PTZ induced concentration-dependent changes in locomotor activity of the 6 dpf larvae characteristic of seizure activity, the effects of prior embryonic exposures to pro- or anticonvulsant compounds on this activity appeared generally unremarkable.