Conditioned taste aversion (CTA) is a form of associative learning in which an animal avoids and reacts aversively to the taste of a food that has previously been paired with illness. CTA has been described in many species, from invertebrates to human, and has important clinical implications in drug and radiation therapies. It may also serve as a model for behavioral plasticity and altered responsiveness in ingestive behaviors, such as are seen in eating disorders. We have recently discovered that the expression of a CTA previously acquired by pairing intraoral infusions of 5% sucrose with lithium chloride is correlated with the expression of the immediate-early gene c-Fos in the medial intermediate region of the nucleus of the solitary tract (iNTS) in the rat. One recent experiments have demonstrated that the induction of c-Fos in the iNTS appears to be a specific and quantifiable neuronal correlate of CTA expression. In this proposal, we hypothesize that c-Fos expression reveals functionally important brain sites mediating CTA expression, and that c-Fos expression in at some of these sites may play a physiological role in CTA acquisition and expression. We will characterize the time course and anatomical distribution of c-Fos expression in the rat brain by in situ hybridization and immunohistochemistry induced by intraoral infusions of sucrose before and after CTA acquisition and after LiC1 injection to identify neuronal populations activated by conditioned and unconditioned stimuli. We will then make fiber-sparing, excitotoxic lesions directed at 1) novel brain sites we have identified the express c-Fos after CTA expression and 2) brain sites previously demonstrated in earlier studies to be required for CTA. Alterations in CTA expression induced by lesions will be measured by quantifying intake, taste reactivity, and c-Fos expression. This proposal presents a novel approach to understanding CTA by attempting to correlate the effects of fiber-sparing lesions on intake and taste reactivity (to distinguish passive avoidance from active rejection) with the effects of the lesion on the pattern of c-Fos expression. Our working hypothesis is that changes in the pattern of c-Fos expression reveal changes in the properties of the network involved in CTA. These experiments will contribute to an understanding of the neural pathways and molecular mechanisms underlying acquired changes in food preferences that occur and may contribute to understanding the pathology of ingestive behaviors, such as occur in obesity, anorexia nervosa, and bulimia nervosa.
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