The objectives of this proposal are two-fold. The primary objective is to evaluate the effects of a series of toxic metals on the olfactory system, using behavioral, biochemical, and morphological endpoints. In order to achieve this goal it is necessary to develop a methodology for the study of sensory neurotoxicology, with the focal point being olfaction. The second objective, based upon the olfactory system's unique capacity of neuronal reconstitution, is to study recovery of function in the olfactory system after toxic insult. To aid in achieving these goals, olfactory function as measured by changes in detection thresholds will be evaluated in rats by the use of a conditioned suppression paradigm. Thresholds will be obtained prior to exposure to the toxic metals and monitored on a regular basis throughout the exposure and recovery period. In addition, assessment of a number of biochemical parameters will be undertaken at specified intervals to study the effects of toxic metal exposure on dopamine function. Both high performance liquid chromatography and a synaptosomal preparation will be employed in this phase of the research. Measurement of carnosine transport will also be used to provide an estimate of the functional integrity of the system. Histological examination will be conducted at various points in time, using both light and electron microscopy, to evaluate morphological alterations within the system and for comparison with the behavioral and biochemical indices. Toxic metals to be studied include trimethytin (TMT), cadmium (Cd), and nickle subsulfide (NS). These three compounds were selected since each produces damage to some part of the olfactory system and each has been associated with dysfunction in the olfactory system. Exposure to Cd and NS will be by inhalation; exposure to TMT will be via the oral route. This research will not only provide information concerning the toxic effects of these metals on a sensory system, specifically olfaction, but will also provide further insight as to how recovery of function occurs within the central nervous system after toxic insult.
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