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%的美国人继续吸烟。 其中一个因素介导发病，持续和复发，特别是在妇女中，是它的体重调节作用。 虽然已经在动物模型中证明，尼古丁（吸烟的活性成分）在停止尼古丁给药后会导致体重减轻和随后的体重增加，但导致这种效应的机制尚未阐明。 本申请提出了旨在鉴定有效的食欲化合物神经肽Y（NPY）在这些效应中的作用的实验。 已知当注射到下丘脑的室旁核（PVN）中时，NPY显著增强动物的食物摄取和碳水化合物的生化利用，并且最近已显示在尼古丁施用期间改变。 在拟议的实验中，通过Alzet泵给药的尼古丁将输注14天，然后突然停止（泵停药）。 拟议的一组实验将确定NPY在急性、慢性和尼古丁后阶段对尼古丁的不同喂养、代谢和性别影响。这些技术将有助于描述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.