HYPOTHALAMIC NEUROTRANSMITTER SYSTEMS & EATING BEHAVIOR

众所周知，大脑中的多肽可以调节饮食行为和身体 体重增加。这项提案将集中于一种特定的多肽，神经肽 Y(NPY)，它在大脑中非常丰富，被发现是 在刺激进食行为方面尤其有效 物种。而有证据表明，NPY可能具有选择性 对碳水化合物摄取的刺激作用和神经肽Y 在下丘脑的合成可能在以下条件下被激活 负能量平衡，该肽在体内的特殊功能 对自然摄食行为的控制仍有待定义。这 构成了拟议的大鼠实验的目的，大鼠有7 明确的目标。这些是：L)要刻画，采用计算机自动化 程序，下丘脑注射NPY激动剂和 拮抗剂对大鼠大量营养素摄入模式的影响；2)使用 中枢注射和损毁技术评估 下丘脑特异性核团在介导NPY作用中的作用 碳水化合物摄入；3)使用生化技术检查 肾上腺切除动物对糖皮质激素、皮质酮的影响 (CORT)，对下丘脑NPY基因表达和NPY水平的影响；4) 应用生化方法研究神经肽Y及其基因的变化 在光/暗周期中，表达与循环皮质醇有关； 5)通过生化和行为测量，检查功能 下丘脑NPY与循环相互作用的意义 CORT，与开始时碳水化合物摄入量的增加有关 6)观察下丘脑NPY、 可能与皮质醇有关，在调节碳水化合物方面很活跃 青春期前的摄入量及其是否导致性别差异 对这种营养的偏好；以及7)检查短期 食物剥夺对下丘脑NPY水平、NPY基因表达和 循环中的科尔特。 这些提议的实验的最终目标是理解 神经性厌食症患者临床表现的意义 或暴食症表现出脑脊液中NPY或相关多肽水平的紊乱， 它们与脑脊液皮质醇水平的变化以及 碳水化合物摄入量的变化。

Peptides in the brain are known to modulate eating behavior and body weight gain. This proposal will focus on a specific peptide, neuropeptide Y (NPY), which is very abundant in the brain and is found to be particularly potent in stimulating eating behavior in a variety of species. While evidence indicates that NPY may have a selective stimulatory effect on the ingestion of carbohydrate and that NPY synthesized in the hypothalamus may be activated under conditions of negative energy balance, the specific function of this peptide in controlling natural ingestive behavior remains to be defined. This constitutes the purpose of the proposed experiments in rats, which have 7 Specific Aims. These are: l) to characterize, using computer-automated procedures, the effects of hypothalamic injection of NPY agonists and antagonists on the rats' patterns of macronutrient intake; 2) to use central injection and lesion techniques to evaluate the importance of specific hypothalamic nuclei in mediating the action of NPY on carbohydrate ingestion; 3) to employ biochemical techniques to examine, in adrenalectomized animals, the impact of the glucocorticoid, corticosterone (CORT), on NPY gene expression and NPY levels in the hypothalamus; 4) to investigate using biochemical procedures shifts in NPY and its gene expression, in relation to circulating CORT, across the light/dark cycle; 5) to examine, through biochemical and behavioral measures, the functional significance of the interaction between hypothalamic NPY and circulating CORT, in relation to the rise in carbohydrate ingestion at the onset of the active dark period; 6) to investigate whether hypothalamic NPY, possibly in association with CORT, is active in modulating carbohydrate intake before puberty and whether it contributes to gender differences in preference for this nutrient; and 7) to examine the impact of short-term food deprivation on hypothalamic NPY levels, NPY gene expression and circulating CORT. The ultimate goal of these proposed experiments is to understand the significance of the clinical findings that patients with anorexia nervosa or bulimia exhibit disturbances in CSF levels of NPY or a related peptide, which are associated with alterations in CSF cortisol levels as well as changes in carbohydrate ingestion.