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，食物摄入的自然模式， 食欲不受干扰，自由行为的大鼠。 利用各种 然后，我们建议研究神经化学 这些自然模式的基质，最终目标是 将这些发现与神经化学紊乱联系起来， 临床饮食失调 先前的研究表明， 动物有能力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， 这表明，参与和互动， 下丘脑神经递质在这个过程中。 的重点 研究是关于α-去甲肾上腺素能和肾上腺素能系统， 大脑 具体来说，我们建议调查的假设 下丘脑内侧的去甲肾上腺素和肾上腺素 在控制碳水化合物摄取方面具有拮抗作用， 尤其是在活动周期开始时， 在抑制蛋白质含量的同时增加碳水化合物含量 摄入量和血清素产生正好相反的模式， 方面的影响. 对于研究计划的第一个实验，我们 建议持续监测自然夜间模式， 在完整的、自由进食的大鼠中大量营养素摄入。 通过 外周和中心药物注射，实验2将提供 系统分析外源性下丘脑 去甲肾上腺素能和肾上腺素能刺激对夜间模式的影响 摄入量 基本假设将直接在 实验三，通过微透析和HPLC程序， 测量内源性下丘脑释放的去甲肾上腺素， 5-羟色胺同时连续测量大量营养素 摄入 为了理解这些重要作用， 神经递质在正常的进食行为，我们将研究在 实验4，通过下丘脑注射神经毒素， 内源性去甲肾上腺素的相对选择性消耗 和血清素，对大量营养素摄入的时间模式， 在实验5中，我们将类似地分析 肾上腺激素皮质酮，这是已知的相互作用， 下丘脑单胺系统，最后，实验6将测试， 通过短暂的食物剥夺，老鼠的行为模式 补偿性喂养，相对于正常和操作 下丘脑神经递质活性的模式， 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.