DIETARY AMINO ACID DISPROPORTION--NEURAL RESPONSES

描述(改编自《调查者摘要》)：饮食失调 摄入量与发病率和死亡率增加有关。这个 与氨基酸(AA)比例失调的营养问题有关 有厌食症的反应。对机制有更好的理解 潜在的这些反应可能会对某些厌食症和 提供有关AA在控制食物摄入量方面的作用的信息。 将限制性(LIM)氨基酸替换为已知的精确脑区 厌食反应所必需的将改善进食抑制 这表明在那里可以感觉到极限AA的下降。这个 进食不平衡AA的动物体内5-羟色胺(5-HT)系统也被激活 饮食，以及重要的是，阻断5HT3受体可以显著地 增加这些饮食的摄入量。然而，尽管有相当多的证据 倾向于将大脑作为AA失衡的控制部位，最近 初步研究表明，5HT3拮抗剂可能作用于 周围部位在治疗再生障碍性贫血相关厌食症中的作用 不平衡。对本提案的研究旨在探讨 进一步了解5HT系统的作用，试图了解如何以及在哪里 它的作用是调节对AA失衡的厌食反应。特定的 目标1解决5-羟色胺系统在这种营养中的特异性 模特。专门的目标2是确定活动的轨迹 5HT3系统在此模型中。具体目标3是检验假设 (A)条件性味觉厌恶(CTA)的形成可能是最终结果 AA失衡的进食抑制的共同途径，以及(B) 5HT3受体参与了这方面的反应。最后，一个 低迷摄食反应机制的研究 将使用一种神经化学物质作为特定目标#4启动AA过量 调查与早前使用的类似，但存在AA失衡的不足 模特。这些研究将利用纯化的L-AA作为蛋白质 在定义的饮食中等同，以食物摄入量作为实验结果。 申请者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过量进食时抑郁的潜在机制和 缺乏症。

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.