It has recently been suggested by several studies that environmental exposure to the organophosphate insecticide chlorpyrifos may be a significant public health risk in the U.S. Exposure of children to chlorpyrifos is of special concern because of the potential for disruption of normal brain function and cognitive development. Several studies indicate that the cognitive development of children and laboratory animals may be compromised by early exposure to chlorpyrifos, but the neurochemical and physiological basis for these effects have not been delineated. Studies that are correlative, incorporating both neurochemistry and behavior into their design, are desirable for addressing this issue. Some have been attempted, but they have not examined cognitive behavior in juvenile laboratory animals. Cognitive behavior, rather than general behavior in laboratory animals, is an important endpoint because it can be used to gain insight into the mechanisms of toxicity that may be relevant to learning abilities in school-aged children.
The specific aims of this research proposal are: 1) To determine the effect of chlorpyrifos on cognitive performance of juvenile rats in the Morris swim task, and 2) To correlate neurochemical changes with behavioral changes in these same juvenile rats that are exposed to chlorpyrifos. A learning index and other performance measures from the Morris task will be correlated to cholinesterase activity and the density of brain cholinergic receptors. Much of the current information on learning and memory in mammals has come from studies with the Morris task. This method has become widely accepted as an excellent measure of learning and memory in laboratory rodents. We, and others have used this paradigm for examining learning and memory in juvenile rats. The inhibition of cholinesterases and the accompanying changes in cholinergic receptors are well-documented and reproducible neurochemical effects of chlorpyrifos exposure. We also have extensive experience with pesticides and these types of neurochemical changes. It has been hypothesized that these neurochemical changes may be related to behavioral changes. Thus, a tremendous opportunity exists to test an integrative neurochemical-behavioral model for studying the developmental neurotoxicity of chlorpyrifos. This study is significant because it is the first to assess the effects of chlorpyrifos on cognitive behavior in the juvenile rat, and the first to determine if neurochemical changes reflect behavioral changes.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Small Research Grants (R03)
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Special Emphasis Panel (ZES1-LKB-C (R1))
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Kirshner, Annette G
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Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
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Jett, D A; Navoa, R V; Beckles, R A et al. (2001) Cognitive function and cholinergic neurochemistry in weanling rats exposed to chlorpyrifos. Toxicol Appl Pharmacol 174:89-98