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Developmental Exposure to a Dopaminergic Toxicant Produces Altered Locomotor Activity in Larval Zebrafish
Citation:
IRONS, T. D., R. C. MACPHAIL, D. L. HUNTER, B. K. PADNOS, AND S. J. PADILLA. Developmental Exposure to a Dopaminergic Toxicant Produces Altered Locomotor Activity in Larval Zebrafish. Presented at the Annual Convention of the Society of Toxicology, Baltimore, MD, March 16 - 19, 2009.
Impact/Purpose:
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Description:
In an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after developmental exposure to various classes of prototypic drugs that act on the central nervous system. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxicant that destroys dopaminergic neurons, causing parkinsonian signs in mammals. Our hypothesis was that exposure of zebrafish embryos/larvae to MPTP would produce locomotor changes reminiscent of the decreased activity seen in studies of MPTP in developing mammals. Zebrafish were exposed to 0.08-50 µM MPTP in a 96-well microtiter plate from 5 hours to 5 days post-fertilization, followed by one washout day. On the sixth day, larvae were evaluated for teratogenic effects (structural alterations); locomotor activity was also assessed during alternating periods of light and darkness (infrared) using video tracking. Developmental exposure to the highest dose of MPTP (50 µM) produced teratogenic changes, as well as hypoactivity. In contrast, a lower non-teratogenic dose of MPTP produced hyperactivity. Therefore, larvae that had been exposed to high doses of MPTP during development showed decreases in motor activity similar to changes noted in mammals and zebrafish; however, the unique finding in the current study is that zebrafish larvae exposed to lower doses of MPTP manifested with hyperactivity. (T.D. Irons is supported by the NIH NIGMS Initiative for Maximizing Student Diversity and the NIEHS National Research Service Award (T32 ES007126). This is an abstract of a proposed presentation; the information does not necessarily reflect Agency policy.)