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Drugs that Target Dopamine Receptors: Changes in Locomotor Activity in Larval Zebrafish
Citation:
Irons, T. D., P. Kelly, D. L. Hunter, R. C. MACPHAIL, AND S. J. PADILLA. Drugs that Target Dopamine Receptors: Changes in Locomotor Activity in Larval Zebrafish. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
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. This includes assessing the acute effects of drugs known to act on the central nervous system, specifically the dopaminergic nervous system.
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 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 light:dark cycle with lights on at 0830 hr. Non-lethal concentrations of both selective (e.g. quinpirole and haloperidol) and nonselective (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. An initial experiment identified the time of peak effect of each drug (20-260 minutes post-dosing, depending on the drug). Locomotor activity was then assessed for a period of 70 minutes in light and dark conditions at the time of peak effect to analyze concentration-dependent effects of the drug. 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 activity. The dose-response profiles of the nonselective drugs were more complex, displaying biphasic 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.]