Zebrafish biogenic amine transporters and behavior in novel environments: Targets of reuptake inhibitors and pesticide action as tools for neurotoxicology research

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.