Adult exposure to insecticides causes persistent behavioral and neurochemical alterations in zebrafish.


Farmers are often chronically exposed to insecticides, which may present health risks including increased risk of neurobehavioral impairment during adulthood and across aging. Experimental animal studies complement epidemiological studies to help determine the cause-and-effect relationship between chronic adult insecticide exposure and behavioral dysfunction. With the zebrafish model, we examined short and long-term neurobehavioral effects of exposure to either an organochlorine insecticide, dichlorodiphenyltrichloroethane (DDT) or an organophosphate insecticide chlorpyrifos (CPF). Adult fish were exposed continuously for either two or 5 weeks (10-30 nM DDT, 0.3-3 μM CPF), with short- and long-term effects assessed at 1-week post-exposure and at 14 months of age respectively. The behavioral test battery included tests of locomotor activity, tap startle, social behavior, anxiety, predator avoidance and learning. Long-term effects on neurochemical indices of cholinergic function were also assessed. Two weeks of DDT exposure had only slight effects on locomotor activity, while a longer five-week exposure led to hypoactivity and increased anxiety-like diving responses and predator avoidance at 1-week post-exposure. When tested at 14 months of age, these fish showed hypoactivity and increased startle responses. Cholinergic function was not found to be significantly altered by DDT. The two-week CPF exposure led to reductions in anxiety-like diving and increases in shoaling responses at the 1-week time point, but these effects did not persist through 14 months of age. Nevertheless, there were persistent decrements in cholinergic presynaptic activity. A five-week CPF exposure led to long-term effects including locomotor hyperactivity and impaired predator avoidance at 14 months of age, although no effects were apparent at the 1-week time point. These studies documented neurobehavioral effects of adult exposure to chronic doses of either organochlorine or organophosphate pesticides that can be characterized in zebrafish. Zebrafish provide a low-cost model that has a variety of advantages for mechanistic studies and may be used to expand our understanding of neurobehavioral toxicity in adulthood, including the potential for such toxicity to influence behavior and development during aging.





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Publication Info

Hawkey, Andrew B, Lilah Glazer, Cassandra Dean, Corinne N Wells, Kathryn-Ann Odamah, Theodore A Slotkin, Frederic J Seidler, Edward D Levin, et al. (2020). Adult exposure to insecticides causes persistent behavioral and neurochemical alterations in zebrafish. Neurotoxicology and teratology, 78. p. 106853. 10.1016/ Retrieved from

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Frederic J. Seidler

Assistant Research Professor Emeritus of Pharmacology & Cancer Biology

We study the effect of drugs, hormones and environmental factors on the intracellular and extracellular biochemical signals that govern the development of mammalian neural tissues, with particular emphasis on the biochemistry and molecular biology underlying control of replication, differentiation, synaptogenesis and onset of synaptic function.  Ongoing projects comprise the following areas: (1) the role of endocrine and neurotrophic factors in transmitter and receptor choice by developing neurons; (2) effects of drugs of abuse, hormonal imbalances, environmental contaminants and fetal/neonatal hypoxia, on nervous system development; (3) control of fetal/neonatal cardiovascular and respiratory function by the immature nervous system, with particular emphasis on parturition and Sudden Infant Death Syndrome; (4) molecular mechanisms of brain dysfunction in the elderly (Alzheimer's Disease and Depression); (5) control of gene expression in developing cells by trophic factors that operate through defined second messenger systems and protooncogenes.
Research is directed toward understanding the interaction of drugs, hormones and environmental factors with the developing nervous system. The role of these factors in mediating development of nerve cells is a major effort as they influence the subsequent structural and functional state of nervous system and its targets. The approach is multidisciplinary. Ongoing projects involve three areas:

1. Mechanisms regulating the development of synapses and the role of endocrine and other trophic factors (i.e. neurotransmitters) in this regulation. Long-term structural and functional consequences of altered development are evaluated.
2. Adverse effects of exogenous agents on nervous system development, emphasizing the identification of mechanisms by which behavioral or physiological injury occurs. Under investigation are: Drugs of abuse (especially cocaine and nicotine), hormonal imbalances, environmental contaminants (pesticides, flame retardants, etc.), food additives, stress, intrauterine growth retardation and hypoxia.
3. Molecular mechanisms of human brain dysfunction in the elderly, specifically Alzheimer's disease and depression.

New directions are concentrating on neurotransmitter and hormonal regulation of cell differentiation and gene expression:
1. Neurotransmitter control of cell differentiation in the central nervous system. The role of transient receptor expression and transduction in effecting the switch from replication to differentiation and the molecular (epigenetic) mechanism underlying control of early immediate genes.
2.  Consequence of early life exposures on subsequent development of adult decease.  Altered vulnerabilities resulting from multiple exposure events (i.e. fetal nicotine x neonatal pesticide).
3.  Establishing in vitro models to explore the mechanisms abnormalities.


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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