PHYSIOLOGICAL PSYCHOLOGY OF MOTIVATED BEHAVIOR

这项研究更新提案的长期目标 科学家奖是为了确定控制 动物和人类的食量。查明这些机制将 允许对它们进行操作以治疗发生在 至少是某些形式的人类肥胖，是暴食症的标志 神经质。 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、大鼠的膳食大小 下丘脑腹内侧部肥胖(VMH)和Zucker(fa/fa)大鼠 与遗传性肥胖有关。该提案的主要目的是衡量 尽可能独立地发挥刺激和满足的作用 蔗糖和脂肪取决于饭菜的大小。这将通过利用 这些影响在肠道中的不同定位--口腔 刺激作用的主要部位，胃，小 肠、肝是产生饱腹感的主要部位。 四个特定的假说被检验--多巴胺能调节 蔗糖和脂肪、迷走神经传入调节的积极增强作用 蔗糖和脂肪在胃里和肚子里的饱腹感 小肠与内源性缩胆囊素的饱腹作用 在小肠和大脑中的作用，以及 5-羟色胺能和雌性激素对大鼠饱腹感的影响 外周缩胆囊素。方法包括假喂，慢性 十二指肠插管，幽门套囊，高效液相-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及其特异性拮抗剂 缩胆囊素。 这些实验的一个普遍主题是寻找差异 在雄性和雌性大鼠之间的效力或机制 控制瘦肉型或神经性或遗传性(FA/FA)肥胖者的膳食数量 啮齿动物。

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.