A Behavioral Test Battery to Assess Larval and Adult Zebrafish After Developmental Neurotoxic Exposure

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Behavioral test batteries are valuable methods which allow outcomes with varying characteristics and neurobiological bases to be assessed and compared in the same animals. This allows investigators to construct a profile of impairments produced by a pharmacological or toxicological challenge, and to propose mechanisms for further study based on those findings. This profile is valuable in the assessment of potentially hazardous substances, including environmental toxicants, drugs of abuse, and other neuropharmacologically active agents. Behavioral tests and batteries have been developed for a number of species, including a relatively recent and growing body of work with the zebrafish, Danio rerio. This chapter discusses the current zebrafish behavioral battery used in our laboratory, and some of the main factors that drove its development. The principal tests include a motility assay for larval fish (6 days post fertilization, dpf), and a battery intended for adolescent (2–3 months) and adult fish (5+ months), which assay sensorimotor, affective, and cognitive-like functions in these fish. Significant progress has been made in the areas of zebrafish neurobehavioral analysis, although further studies, refinements, and task development efforts will be needed to strengthen this approach in the future.






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Edward Daniel Levin

Professor in Psychiatry and Behavioral Sciences

Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. His primary academic appointment is as Professor in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments in the Department Pharmacology and Cancer Biology, the Department of Psychological and Brain Sciences and the Nicholas School of the Environment at Duke. His primary research effort is to understand basic neural interactions underlying cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.

The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learning memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenia, Alzheimer's Disease and Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.

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