This project's ultimate goal is to identify behavioral and neurochemical indices that provide accessible markers of nervous system injury due to exposure to toxic wastes. The proposed indices (behavioral test of [1] diurnal rhythms and [2] cognitive function and [3] nervous system- specific proteins) can be died both in lab animals and in humans. A 3- tiered approach will be used. First, a practical, noninvasive endpoint (homecage activity of rats) will be used for sub-acute dose range- finding. The purpose is to: 1) develop efficient testing strategies for studies measuring behavior nondestructively and then sharing rats with other, destructive projects; 2) identify model toxicants exhibiting specific neurotoxicity by comparing dose-effect functions with other projects; 3) identify toxicant producing correlated changes in behavior and brain proteins. The dose-effect data will be used in tier 2 to plan longer exposures to the more selective toxicants. Endpoints in rats will be complex, learned behavior similar to that studied in humans, and the proteins found to be most promising in tier 1. The purpose is: 1) to focus on toxicants and exposures which affect the rat's complex, learned behavior; 2) to determine whether the correlated changes in brain proteins can also be detected in rat and human serum; and 3) to obtain normative data on the performance of an objective, nonlingual test of cognitive function for use both with humans and with primates. Tier 3 will: 1) refine the cognitive test of ruse in the field and in clinic; 2) study the cognitive function and correlated proteins in selected populations; and 3) use the human data for planning further experiments aimed at questions that can only be asked with animals. model toxicants will be studied in rats uniformly prepared by the exposure core so as to maximize comparison of results with other projects. Positive neurotoxicants (oral exposure to methlymercury or acrylamide; inhalation of toluene or trichloroethylene) will be contrasted with others though to have less specific neurotoxicity (nickel, chromium, cadmium, benzene, etc.).
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