DIET, AROMATIC AMINO ACIDS, AND CNS NEUROTRANSMITTERS

这项竞争性的继续研究计划将在大鼠中研究单餐和长期饮食的蛋白质含量对（a）酪氨酸（TYR）的中枢神经系统（CNS）浓度及其衍生的儿茶酚胺神经递质的合成速率的影响（多巴胺[DA]、去甲肾上腺素[NE]）;和（B）在施用TYR或改变脑中DA或NE神经传递的药理学试剂后动物对膳食蛋白的自我选择。 中枢神经系统酪氨酸代谢率在摄入高蛋白膳食后大幅增加。此外，中枢神经系统酪氨酸代谢率随着慢性蛋白质摄入量的接近而显著下降，并且福尔斯下降到大鼠维持蛋白质需求量以下;在两种饮食条件下，酪氨酸代谢率羟基化率（儿茶酚胺合成的指标）发生平行变化。 这项建议将建立在这些发现的基础上，使用一种结合行为-神经化学的方法。 在行为研究中，我们将评估TYR给药是否改变大鼠对膳食蛋白质的选择。 如果是，我们将确定涉及的DA和/或NE受体。 在生化研究中，我们将确定哪些儿茶酚胺受到影响（DA，NE或两者）通过蛋白质摄入量的变化，它们发生的大脑区域（主要是两个NE和DA-含有下丘脑核参与食物摄入控制，室旁核和外侧穹窿周围下丘脑），和TYR的关系，由膳食引起的DA和NE变化与由慢性膳食蛋白质摄入量改变引起的DA和NE变化。 一个相关的焦点将是确定蛋白质摄入量低于需求量的减少是否也会减少脑外（交感神经，肾上腺髓质）的儿茶酚胺产生和释放，如果是这样，交感神经功能是否下降。 第三个重点将是大脑组氨酸，据报道，当蛋白质摄入福尔斯低于需求水平时，组氨酸会显著增加。 我们将检查是否发生这种变化;如果是这样，它们是否会增强脑组胺（由组氨酸合成的递质）的合成/周转;如果发生组胺增加，它们是否会影响对总热量和/或蛋白质的食欲（使用自我选择范式）。 这些研究将采用生物化学、药理学、生理学和行为学方法。 动物（和人类）必须满足其对蛋白质的营养需求，以生存和繁殖。 因此，监测需求值附近的蛋白质摄入水平的能力是重要的。 这些研究的结果应该表明酪氨酸-儿茶酚胺（DA，NE）和/或组氨酸-组胺的关系是否提供了潜在的途径，通过这些途径大脑可以接收有关蛋白质摄入的信息，如果是这样的话，大脑是否使用这样的信号来调节动物摄取蛋白质的驱动力。

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.