DIETARY AMINO ACID DISPROPORTION--NEURAL RESPONSES

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DESCRIPTION (Adapted from Investigator's Abstract): Disorders of food intake are associated with increased morbidity and mortality. The nutritional problem of amino acid (AA) disproportionality is associated with anorectic responses. A better understanding of the mechanisms underlying these responses may yield insight into certain anorexias and provide information about the role of AA's in the control of food intake. Replacement of the limiting (Lim) AA into a precise brain area known to be essential for the anorectic response will ameliorate the feeding depression suggesting that the decrease in the limiting AA is sensed there. The serotonin (5HT) system is also activated in animals eating imbalanced AA diets, and importantly, blockade of the 5HT3 receptor can dramatically increase intake of these diets. However, in spite of considerable evidence favoring the brain as the site of control in AA imbalance, recent preliminary studies suggest that the 5HT3 antagonist may be acting at a peripheral site in remediating the anorexia associated with an AA imbalance. The studies of the present proposal are designed to explore the role of the 5HT system further, in an attempt to understand how and where it functions to mediate the anorectic response to AA imbalance. Specific Aim 1 addresses the specificity of the 5HT system in this nutritional model. Specific Aim 2 is to determine the locus of the activity of the 5HT3 system in this model. Specific Aim 3 is to test the hypotheses that (a) the development of a conditioned taste aversion (CTA) may be the final common pathway in the feeding depression with AA imbalance, and (b) the 5HT3 receptor is involved in this aspect of the response. Finally, an investigation of the mechanisms underlying the depressed feeding responses to AA excess will be initiated as Specific Aim #4, using a neurochemical survey similar to that used earlier with deficiency in the AA imbalance model. These studies will utilize purified L-AA's as the protein equivalent in defined diets, with food intake as the experimental outcome. The applicant will use neurochemical measurements, neuroanatomical lesions and neuropharmacological interventions as tools for determining the mechanisms underlying the depression in feeding with AA excess and deficiency.