EFFECTS OF NICOTINE ON NPY FEEDING AND METABOLISM

虽然有大量关于吸烟对健康有害影响的信息，但大约26%的美国人仍在吸烟。影响发病、持续和复发的因素之一，特别是在女性中，是其体重调节作用。尽管在动物模型中已经证明，吸烟中的活性成分尼古丁在戒烟后会导致体重减轻和随后的体重增加，但这种影响的机制尚未阐明。本申请提出的实验旨在确定一种有效的产氧化合物，神经肽Y （NPY）在这些作用中的作用。当将NPY注射到下丘脑室旁核（PVN）时，已知NPY可显著增强动物的食物摄入和碳水化合物的生化利用，最近有研究表明，在给药期间，NPY会发生改变。在拟议的实验中，尼古丁通过Alzet泵注入14天，然后突然停止（泵外植）。拟议的一组实验将确定NPY在急性、慢性和后尼古丁期对尼古丁的不同喂养、代谢和性别影响。这些技术将有助于表征NPY在尼古丁的体重调节作用中的作用，以及它如何影响食物摄入和代谢。

While there is extensive information on the deleterious effects of smoking on health, approximately 26 percent of Americans continue to smoke. One of the factors mediating onset, continuance and relapse, particularly in women, is its weight-moderating effects. Though it has been demonstrated in animal models, that nicotine, the active ingredient in smoking, produces weight loss and subsequent weight gain following cessation of nicotine administration, mechanisms responsible for this effect have yet to be elucidated. This application proposes experiments designed to identify the role of a potent orexigenic compound, neuropeptide Y (NPY), in these effects. NPY is known to significantly potentiate food intake and biochemical utilization of carbohydrates in animals when injected into the paraventricular nucleus (PVN) of the hypothalamus, and has been recently shown to be altered during nicotine administration. In the proposed experiments, nicotine, administered via Alzet pumps, would be infused for 14 days followed by an abrupt cessation (pump explantation). The proposed set of experiments will identify the differential feeding, metabolic and gender effects of NPY on nicotine over acute, chronic and post-nicotine phases. These techniques will help to characterize the role of NPY in the weight-moderating effects of nicotine as well as how it affects food intake and metabolism.