The superfund site at Massena, New York, contains high concentrations of polychlorinated biphenyls (PCBs) which are known to cause serious neurobehavioral deficits in animals and humans. The mechanisms of neurobehavioral effects of PCBs are not known, but previous work has led to the hypothesis that ortho-substituted PCBs have selective action on the brain, resulting in a depletion of the neurotransmitter, dopamine. We propose 1) to determine: (a) the congener profile of PCBs in the nervous systems of several classes of animals collected from the superfund site; (b) determine if dopamine levels are reduced in the brain; and (c) determine the effects of exposure on several simple reflexes. 2) continue use of the marine mollusc, Aplysia, to experimentally test the hypothesis that only ortho-substituted PCBs contribute to the loss of brain dopamine and 3) evaluate the relative contribution of the reduction of brain dopamine as compared to non-specific interactions of PCBs with membrane lipids as the basis for the neurobehavioral changes which have been observed in this invertebrate as well as higher mammals and man. Aplysia is ideal for this study in many regards. Exposure of Aplysia to a broad spectrum mixture of 68 PCBs results in righting reflex retardation (RRR), dopamine level reduction (DLR), and preferential bioconcentration of 6 ortho-substituted congeners in the nervous system. Exposure to a single neurophilic congener, 2,4,4' trichlorobiphenyl, mimics the neurobehavioral effects of the mixture. The critical neurons and neural circuits mediating RRR and dopamine neurons are identifiable in Aplysia. They will be exposed to graded doses of individual or groups of neurophilic ortho PCBs, non- neurophilic ortho-PCBs, non-ortho coplanar PCBs, and extracts from the superfund site in order to determine: 1) the relative contributions of each congener type or group to RRR and DLR; 2) the dose/effect and structure/activity relationships of congeners producing RRR and DLR; and 3) the neurobehavioral effects of exposure to extracts from the superfund site. Effects of non-planar and planar PCBs will also be compared at the neuronal level. Changes in membrane biophysical properties, ionic conductances, current-voltage relationships, axonal conduction velocity, response to neurotransmitters, and synaptic transmission will be determined in identifiable homologous reflex and dopamine neurons exposed in vivo and in vitro to non-planar and planar PCBs. Taken together, these results will elucidate the mechanism of PCB action on fundamental processes underlying signalling and integrative capacities of the nervous system in Aplysia and validate the applicability of these mechanisms to other animals, including those associated with the superfund site.
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