DIETARY AMINO ACID DISPROPORTION--NEURAL RESPONSES

描述（改编自研究者摘要）：食物障碍 摄入与发病率和死亡率增加有关。 的 氨基酸（AA）缺乏的营养问题与 厌食反应。 更好地理解机制 作为这些反应的基础，可能会让我们深入了解某些不稳定性， 提供有关AA在控制食物摄入方面的作用的信息。 将限制性（Lim）AA替换为已知的精确大脑区域， 对厌食反应至关重要的药物将改善摄食抑制 这表明在那里检测到极限AA的降低。 的 5-羟色胺（5-HT）系统也被激活的动物吃不平衡的AA 饮食，重要的是，阻断5 HT 3受体可以显着 增加这些饮食的摄入量。 然而，尽管有大量证据表明， 支持大脑作为AA不平衡的控制部位， 初步研究表明，5-HT 3拮抗剂可能以 治疗AA相关厌食症的外周部位 不平衡 本建议的研究旨在探讨 5 HT系统的作用，进一步，试图了解如何和在哪里 其功能是调节对AA失衡的厌食反应。 具体 目的1解决了这种营养中5 HT系统的特异性， 模型 具体目标2是确定活性位点， 5 HT 3系统在此模型中。 具体目标3是检验以下假设： (a)条件性味觉厌恶（CTA）的发展可能是最终的 AA不平衡的摄食抑制中的共同途径，和（B） 5 HT 3受体参与了这方面的反应。 最后通过一个 摄食反应抑制机制的研究 AA过量将作为特定目标#4启动，使用神经化学物质 调查类似于先前使用的AA失衡不足的调查 模型 这些研究将利用纯化的L-AA作为蛋白质 在定义的饮食中等效，以食物摄入量作为实验结果。 申请人将使用神经化学测量、神经解剖学损伤 和神经药理学干预作为确定 AA过量喂养引起抑郁的机制， 缺陷

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.