The investigator asserts that the ingestive reaction to taste stimuli is a complex interaction among three processes, taste neophobia, defined as an innate fear of novel tastes, gastrointestinal malaise, a normal phenomenon that occurs following ingestion of poisonous substances, and learning, the associative link between taste and malaise. The investigator has chosen the conditioned taste aversion (CTA) paradigm as a model and now proposes to investigate the role of the parabrachial nuclei (PBN) in CTA learning. The PBN is strategically important in this response because it appears to be part of both the ascending and the descending pathways through the brainstem involved in the gustatory and visceral afferent systems. In previous work, the investigator has replicated and extended the work of others showing that PBN lesions disrupt the ability of animals to form CTAs. Importantly, he has also found that PBN lesions appear to abolish taste neophobia, and he argues that non-neophobic animals are not able to form CTAs because they do not perceive novel tastes as potentially dangerous. He therefore hypothesizes that the apparent inability of PBN-lesioned rats to form a CTA, rather than being due to an inability to form associative connections between tastes and noxious events, is actually due to a lesion-induced misperception of the tastant. In this regard, it is well established that intact animals do not easily form CTAs well to familiar (i.e., known to be safe) tastants. Proposed experiments will use ibotenic acid lesions of selected areas of the PBN to test various aspects of this hypothesis. In one series of experiments, animals with PBN lesions will be assessed for neophobia to a variety of stimuli including several tastants, the hypothesis being that such animals will have a generalized neophobic deficit. Non- gustatory stimuli will be used in addition to several tastants. In other experiments, the ability of PBNx animals to perceive tastants will be assessed, as will their ability to react appropriately (i.e., to demonstrate an """"""""alerting response"""""""") to the tastants. In another series of experiments, animals with PBN lesions will be subjected to more rigorous and more prolonged protocols for developing CTAs, the hypothesis being that the same effort will be required to form an aversion to a novel tastant in PBNx rats as is normally required to form an aversion to a familiar tastant in controls. Finally, the investigator will vary the relative familiarity of the subjects to various tastants prior to attempting to condition aversions in order to maximize or minimize the differences between PBNx and control animals. In all of the proposed experiments and paradigms, there will be an assessment of the relative contributions of the two major divisions of the PBN. The medial PBN is the gustatory portion and the lateral PBN is the visceral afferent portion. Therefore, all experiments will be run in parallel, with one arm investigating the medial and the other the lateral PBN. For most conditions the investigator will also include assessments of both acute (i.e., 15-minute) and 24-hour intakes to assess both short-term gustatory and post-ingestive influences. In pilot work, the investigator has demonstrated both the lack of neophobia in medial PBNx rats, and their (albeit lessened) ability to form a CTA. He has also replicated the effects of others with electrolytic lesions of the PBN and obtained comparable findings with locally applied ibotenic acid. He has also provided data that PBNx rats can discriminate tastants, and that they experience the acute toxic effects of lithium chloride.
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