Zebrafish Models in Neurobehavioral Research pp 181-209 | Cite as
Zebrafish Biogenic Amine Transporters and Behavior in Novel Environments: Targets of Reuptake Inhibitors and Pesticide Action as Tools for Neurotoxicology Research
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Abstract
Central monoamine systems (e.g., dopamine, serotonin, norepinephrine) are associated with motivation, locomotion, social behavior, emotion, and mood. Biogenic amine transporters regulate neurotransmission by removing neurotransmitters from synapses and extracellular fluid. Despite evolutionary divergence, teleost fish and mammalian transporter proteins appear similar, particularly at active binding sites. However, it is not clear if the similarities extend to functional responses, reuptake-inhibiting drugs, or involvement in delayed neurotoxic responses to pesticide exposures. Under certain exposure conditions, alterations in expression and function of these transporters may be more sensitive biomarkers of pesticide exposure or neurodegenerative disease risk than acetylcholinesterase inhibition. Zebrafish (Danio rerio) behavioral assays targeting associative responses such as anxiety are useful as pharmacological and toxicological screens, or for studying modulation of behavior by central neurotransmitter systems. In novel environments, zebrafish go to tank bottoms and dark backgrounds, a stereotypical behavior (attributed to predator anxiety) forming the basis of the novel light/dark aquatic plus maze characterized in this chapter. Such behavioral paradigms are an essential component to establish zebrafish as pharmacological and toxicological research models. Herein adult zebrafish are exposed to reuptake inhibitors and representative organochloride, organophosphate, or pyrethroid pesticides at 1 μg day−1 for 21 days, tested for anxious response in the light/dark plus maze, then assayed for dopamine and serotonin transporter density by radioligand binding. Exposures to these compounds variably affect dopamine and serotonin transporter density and alter behavior in the maze as compared to controls.
Key words
Dopamine serotonin norepinephrine monoamine systems amine transporters acetylcholinesterase inhibition mammalian homology SERT DAT transporter mechanisms Parkinson’s disease pesticide light-dark plus-maze expression regulation toxicologyNotes
Acknowledgments
This study was funded by a NIOSH ERC Pilot Project research training grant awarded by the Southwest Center for Occupational and Environmental Health at the University of Texas School of Public Health in Houston (Grant No. T42CCT610417 from NIOSH/CDC to SWCOEH). I would like to thank Dr. Alan Frazer for sponsoring this research in his laboratory at UTHSCSA, Ezra Scientific LLC for technical assistance in developing and building the zebrafish offset cross maze, and Jim Sackerman, Ngoc Nhung Nguyen, Adam Long, Kelly Lawless, and Dr. Bob Benno at William Paterson University, New Jersey, for their technical assistance and intellectual input in validating the dive tank and light/dark plus maze tests.
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