HYPOTHALAMIC NEUROTRANSMITTER SYSTEMS & EATING BEHAVIOR

这个项目的一个基本目标是详细分析，使用 自动化程序，食物摄取的自然模式和 不受干扰、行为自由的老鼠的食欲。利用多样性 程序，然后我们建议研究神经化学物质 这些自然图案的底物，最终目标是 将这些发现与神经化学障碍联系起来 临床进食障碍。之前的研究已经证明 动物能够在体内选择适当的常量营养素 对生理信号的反应。此外，现在有证据表明 浮现的暗示…的参与和互动的 下丘脑在这一过程中的神经递质。这件事的重点是 中国对α-去甲肾上腺素和5-羟色胺能系统的研究 大脑。具体地说，我们建议调查这一假设 下丘脑内侧的去甲肾上腺素和5-羟色胺 在控制碳水化合物摄取方面有拮抗作用， 尤其是在活动周期开始时，使用去甲肾上腺素 在抑制蛋白质的同时增加碳水化合物膳食 摄入量和5-羟色胺产生的模式正好相反 效果。在研究计划的第一次实验中，我们 建议持续监测北极熊的自然夜间模式 在完整的、自由喂养的大鼠中摄入大量营养素。穿过 外周和中枢药物注射，实验2将提供一种 外源性下丘脑影响的系统分析 去甲肾上腺素和5-羟色胺能刺激对夜间模式的影响 摄取。然后，基本假设将直接在 实验3，通过微透析和高效液相程序，将 测量下丘脑内源性去甲肾上腺素和 5-羟色胺与常量营养素的连续测定 入口处。要了解这些因素的基本作用 正常进食行为中的神经递质，我们将在 实验四，通过注射下丘脑神经毒素，对 相对选择性地消耗内源性去甲肾上腺素 和5-羟色胺对大量营养素摄入的时间模式的影响，以及 在实验5中，我们将类似地分析 肾上腺激素皮质酮，已知与 下丘脑单胺系统，最后，实验6将测试， 通过短暂的食物缺乏暴露，大鼠的模式 补偿性喂养，与正常喂养和人工喂养有关 下丘脑神经递质活性的模式和 循环皮质酮水平。

A basic goal of this project is to analyze in detail, using automated procedures, the natural patterns of food intake and appetite of undisturbed, freely behaving rats. Utilizing a variety of procedures, we then propose to investigate the neurochemical substrates of these natural patterns, with the ultimate goal of relating these findings to neurochemical disturbances seen in clinical eating disorders. Previous studies have demonstrated that animals have the ability to select appropriate macronutrients in response to physiological signals. Moreover, evidence is now emerging to suggest the involvement and interaction of hypothalamic neurotransmitters in this process. The focus of this research is on alpha-noradrenergic and serotonergic systems in the brain. Specifically, we propose to investigate the hypothesis that norepinephrine and serotnoin in the medial hypothalamus have antagonistic effects in the control of carbohydrate ingestion, particularly at the onset of the active cycle, with norepinephrine acting to enhance carbohydrate meals while suppressing protein intake, and serotonin producing precisely the opposite pattern of effects. For the first experiment of the research plan, we propose to monitor continuously the natural nocturnal patterns of macronutrient ingestion in intact, freely feeding rats. Through peripheral and central drug injections, Experiment 2 will provide a systematic analysis of the impact of exogenous hypothalamic noradrenergic and serotonergic stimulation on nocturnal patterns of ingestion. The basic hypothesis will then be tested directly in Experiment 3, which via microdialysis and HPLC procedures, will measure endogenous hypothalamic release of norepinephrine and serotonin simultaneous to continuous measures of macronutrient intake. To understand the essential role of these neurotransmitters in normal feeding behavior, we will examine in Experiment 4, via hypothalamic neurotoxin injections, the impact of a relatively selective depletion of endogenous norepinephrine and serotonin, on temporal patterns of macronutrient intake, and in Experiment 5, we will similarly analyze the involvement of the adrenal hormone corticosterone, which is known to interact with hypothalamic monoamine systems, Finally, Experiment 6 will test, through brief exposures to food deprivation, the rats' patterns of compensatory feeding, in relation to normal and manipulated patterns of hypothalamic neurotransmitter activity and circulating corticosterone levels.