PHYSIOLOGICAL PSYCHOLOGY OF MOTIVATED BEHAVIOR

动机行为的生理心理学

• 批准号: 3075565
• 负责人: GERARD P SMITH
• 金额: $ 10.54万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-03-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3075565
• 关键词: anorexic agent; autoradiography; bulimia nervosa; cholecystokinin; eating; genetic strain; hereditary hyperglycemic obesity; high performance liquid chromatography; laboratory rat; nutrition related tag; overeating; reinforcer; satiations; sex hormones; vagotomy

The long-term objective of this proposal for renewal of a Research Scientist Award is to identify the biological mechanisms that control meal size in animals and humans. Identification of these mechanisms will permit manipulation of them for therapy of the hyperphagia that occurs in at least some forms of human obesity and is a hallmark of bulimia nervosa. The current proposal is designed to analyze the effect of food stimuli acting primarily preabsorptively on meal size in normal rats, in rats with ventromedial hypothalamic obesity (VMH), and in Zucker (fa/fa) rats with genetic obesity. The major aim of the proposal is to measure as independently as possible the stimulating and satiating effects of sucrose and fat on meal size. This will be done by exploiting the differential localization of these effects along the gut -- the mouth is the predominant site for the stimulating effect, and the stomach, small intestine, and liver are the predominant sites for the satiating effect. Four specific hypotheses are tested -- dopaminergic mediation of the positive reinforcing effect of sucrose and fat, vagal afferent mediation of the satiating effect of sucrose and fat in the stomach and in the small intestine, and the satiating effect of endogenous cholecystokinin in the small intestine and in the brain, and the modulating effects of serotonergic and female sex hormones on the satiating effect of peripheral cholecystokinin. Methods include sham feeding, chronic duodenal catheterization, pyloric cuff, HPLC-electrochemical detection, radiofrequency lesion, selective afferent and efferent vagotomy, quantitative receptor autoradiography, and specific -antagonists of cholecystokinin. A pervasive theme of these experiments is to search for differences between male and female rats in the potency or kind of mechanisms that control meal size in lean or neurologically or genetically (fa/fa) obese rodents.

本研究更新提案的长期目标 科学家奖旨在确定控制的生物机制 动物和人类的膳食量。 识别这些机制将 允许操纵它们来治疗发生在 至少存在某些形式的人类肥胖，并且是贪食症的一个标志 紧张。 目前的提案旨在分析食物刺激的影响 主要作用于正常大鼠和大鼠的预吸收膳食量 腹内侧下丘脑肥胖 (VMH) 和 Zucker (fa/fa) 大鼠 患有遗传性肥胖。 该提案的主要目的是衡量 尽可能独立地发挥刺激和饱腹感 蔗糖和脂肪对膳食量的影响。 这将通过利用 这些效应沿肠道的差异定位——口腔 刺激作用的主要部位是胃，小 肠道和肝脏是产生饱腹感的主要部位。 测试了四个具体假设——多巴胺能介导 蔗糖和脂肪的正强化作用，迷走神经传入介导 蔗糖和脂肪在胃和胃中的饱腹感 小肠，以及内源性胆囊收缩素的饱足作用 在小肠和大脑中，以及调节作用 血清素和女性性激素对饱腹感的影响 外周胆囊收缩素。 方法包括假喂养、慢性 十二指肠插管、幽门套囊、HPLC-电化学检测、 射频损伤、选择性传入和传出迷走神经切断术、 定量受体放射自显影术和特异性拮抗剂 胆囊收缩素。 这些实验的一个普遍主题是寻找差异 雄性和雌性大鼠之间的效力或机制类型 控制瘦肉或神经性或遗传性（fa/fa）肥胖的膳食量 啮齿动物。