polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are widespread environmental contaminants that tend to accumulate in aquatic ecosystems and are known to be neurotoxic. Maternal consumption of fish or marine mammals high in PCBs and/or MeHg has been associated with neurobehavioral deficits in children. Recent evidence from laboratory studies suggests that MeHg and PCBs may be acting in an additive or synergistic fashion to produce some of these effects. Specifically, MeHg appears to potentiate PCB-induced reduction in brain dopamine. The potential behavioral consequences of this are unknown. Hmong and Laotian refugees in northeastern Wisconsin are at risk of elevated PCB and MeHg exposure because a large percentage of them cash and eat fish from the Fox river and other contaminated waters. The proposed animal studies are designed to complement Project 1, which will evaluate neurological outcomes in Hmong and Lao children born to mothers who regularly eat locally caught fish. Long Evans rats will be used as an animal model to characterize in detail the cognitive, motor and sensory effects of exposure to PCBs alone, MeHg alone, or PCBs and MeHg in combination. Congener specific fish contaminant data will be used for formulate a PCB mixture that models the PCB congener profile in Fox River fish as closely as possible. Data on the levels of MeHg that best models the ratio of PCBs to MeHg present in the fish. In depth analyses of the behavioral response data will be used to identify the types of error patterns or deficits that contribute to poor performance on specific behavioral tasks. Pharmacological challenges with dopamine agonists and antagonists will be used to gain a better understanding of the role of change sin dopamine function in mediated specific PCB- and MeHg-related behavioral impairments. Project 3 will complement these studies by investigating specific dopamine-related mechanisms through which PCBs and MeHg could be acting to alter behavioral function. The results of these animal experiments will be used to guide the selection of behavioral and sensory endpoints that should be assessed in the Hmong and Laotian children exposed to PCBs through maternal consumption of Fox River fish.
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