This competing continuation proposal will study in rats the effect of the protein content of single meals and the chronic diet on (a) the central nervous system (CNS) concentration of tyrosine (TYR) and the synthesis rates of the catecholamine neurotransmitters derived from it (dopamine [DA], norepinephrine [NE]); and (b) the animal s self-selection of dietary protein following the administration of TYR or pharmacologic agents that alter DA or NE neurotransmission in brain. Large increases in CNS TYR follow the ingestion of a high-protein meal additionally, CNS TYR drops markedly as chronic protein intake approaches and falls below the rat s maintenance protein requirement; under both diet conditions, parallel changes occur in TYR hydroxylation rate, an index of catecholamine synthesis. This proposal will build on these findings, using a combined behavioral- neurochemical approach. In behavioral studies, we will assess if TYR administration modifies the rat s selection of dietary protein. If so, we will determine the DA and/or NE receptor(s) involved. In biochemical studies, we will determine which catecholamines are affected (DA, NE or both) by changes in protein intake, the brain regions in which they occur (primarily two NE- and DA-containing hypothalamic nuclei involved in food intake control, the paraventricular nucleus and the lateral perifornical hypothalamus), and the relationship of the TYR, DA and NE changes induced by a meal to those caused by alterations in chronic dietary protein intake. A related focus will be to determine if reductions in protein intake below requirement also diminish catecholamine production and release outside the brain (sympathetic nerves, adrenal medulla), and if so, whether sympathetic function declines. A third focus will be brain histidine, which reportedly increases markedly as protein intake falls below requirement levels. We will examine whether such changes occur; if so, whether they enhance the synthesis/turnover in brain histamine, the transmitter synthesized from histidine; and if histamine increases occur, whether they influence appetite for total calories and/or protein (using the self-selection paradigm). Biochemical, pharmacologic, physiological and behavioral approaches will be employed in these studies. Animals (and humans) must meet their nutritional requirement for protein in order to survive and reproduce. An ability to monitor the level of protein intake around the requirement value is thus important. The results of the proposed studies should indicate whether the tyrosine-catecholamine (DA, NE) and/or histidine- histamine relationships provide potential avenues by which the brain can receive information about protein intake, and if so, whether such a signal is employed by the brain to modulate the animal s drive to ingest protein.
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