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.
