MODEL FOR DRUG AND POLLUTION INDUCED DYSGESIA

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The purpose of this proposal is to develop an experimental rat model of dysgeusia to evaluate the induction of taste dysfunction by drugs and pesticides. These studies are important because, at present, there is a paucity of information on the mechanisms by which dysgeusia is induced, and there are no known treatments other than removal of the causative conditions. A possible basis for dysgeusia is alteration of peripheral taste transduction or damage to neural processing pathways caused by medications and pesticides. This project will determine whether drugs and pesticides that cause dysgeusia in humans alter the patterns of taste responses at the level of the nucleus of the solitary tract in rat. The patterns will be determined using a new multiple channel recording method that employs microprobe arrays and neural network signal processing algorithms. Based on preliminary studies using a five-channel system, we expect to be able to record up to 16 channels of neural data simultaneously. Having 16 channels of real-time data will enable us to characterize impaired taste responses in exposed animals and compare the responses with those from unexposed animals. We also expect to quantify the level of exposure by measuring the degree of change in the impaired response. In this study, the effect of four drugs (metronidazole, zidovudine, pentamidine isethionate, and ofloxacin) and one pesticide (chlorpyrifos) on neural coding will be assessed using a multiple electrode inserted into the nucleus of the solitary tract in rats. The drugs and pesticide have been reported clinically to cause dysgeusia in humans. Electrophysiologic recordings will be obtained after direct topical application of these agents to the tongue as well as after oral administration or subcutaneous injection. The objectives of the study are: 1) To demonstrate that specific drugs and pesticides (ones known to cause dysgeusia in humans) alter the neural patterns of taste responses in rat. 2) To quantify the exposure level of these drugs and pesticides to determine the dose-response relationship between the degree of exposure and degree of change in electrophysiologic taste patterns in rat. 3) To validate the study with double-blind comparisons of exposed and unexposed animals.