PHYSIOLOGICAL PSYCHOLOGY OF MOTIVATED BEHAVIOR

本研究更新提案的长期目标 科学家奖是确定控制的生物机制， 动物和人类的膳食量。 确定这些机制将 允许对它们进行操纵，用于治疗发生在 至少是某些形式的人类肥胖，是暴食症的标志 神经。 目前的建议旨在分析食物刺激的影响 在正常大鼠中主要作用于吸收前的膳食量，在大鼠中 腹内侧下丘脑肥胖（VMH）和Zucker（fa/fa）大鼠 遗传性肥胖 该提案的主要目的是衡量， 尽可能独立的刺激和饱足的效果， 蔗糖和脂肪对膳食大小的影响。 这将通过利用 这些影响的差异定位沿着肠道--口腔， 刺激作用的主要部位，以及胃，小 肠和肝是饱腹感的主要部位。 四个具体的假设进行测试-多巴胺能介导的 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效果 小肠和内源性胆囊收缩素的饱足作用 在小肠和大脑中，以及 雌激素能和雌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 十二指肠导管插入术，幽门套囊，高效液相色谱-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和特异性受体拮抗剂 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， 控制瘦型或神经性或遗传性（fa/fa）肥胖者的膳食量 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.