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Drugs Targeting the Dopaminergic Nervous System Alter Locomotion in Larval Zebrafish
Citation:
Irons, T. D., P. Kelly, D. L. HUNTER, R. C. MACPHAIL, AND S. J. PADILLA. Drugs Targeting the Dopaminergic Nervous System Alter Locomotion in Larval Zebrafish. Presented at The Zebrafish Embryo Model in Toxicology and Teratocogy Conference, Karisruhe, GERMANY, September 02 - 03, 2010.
Impact/Purpose:
As part of an effort at the US Environmental Protection Agency to develop a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae.
Description:
As part of an effort at the US Environmental Protection Agency to develop a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae. This includes assessing the acute effects of drugs that are known to act on the central nervous system, specifically the dopaminergic nervous system. Zebrafish larvae (6 days post-fertilization) were maintained in 96-well microtiter plates (1 larva/well) at 26°C and under a 14:10 Iightdark cycle with lights on at 0830 hr. Non-lethal concentrations of both selective (e.g. quinpirole and haloperidol) and non-selective (e.g. apomorphine and butaclamol) dopaminergic agonists and antagonists were administered by immersion. Each drug was screened on individual plates, with a broad range of concentrations and vehicle controls included (e.g. for haloperidol, 0-50 uM concentrations were used and n=12 larvae/concentration/plate). An initial experiment identified the time of peak effect of each drug (20-200 minutes postdosing, depending on the drug). Locomotor activity was then assessed for a period of 70 minutes at the time of peak effect to analyze concentration-dependent effects of the drug. All experiments used a Noldus video activity monitor and Ethovision 3.1 software to track each animal under both visible light or dark (infrared) conditions. All of the drugs tested were found to alter the locomotor activity of 6-day old zebrafish in a dose-dependent manner. The selective agonists and antagonists caused opposing effects on this activity. The dose-response profiles of the nonselective drugs were more complex, displaying biphasic effect patterns. This test has proven to be sensitive for detecting differing patterns of acute behavioral effects produced by drugs that act on the dopaminergic nervous system. This is an abstract of a proposed presentation; the information does not necessarily reflect EPA policy.]