The Impact of Body Weight and Diet on Nicotine Reinforcement in Rats

项目总结 美国食品和药物管理局(FDA)最近被授予监管 香烟中的尼古丁含量降到“不会上瘾”的水平；这样的减少可能会大大减少香烟中尼古丁的数量 增加美国的吸烟者，并改善公共健康。吸烟人口是异质性的，而且确实是 很可能一部分吸烟者对香烟中尼古丁含量的减少反应较差。证据 建议食用高热量饮食(即高脂肪或高糖分的食物)和提高身体素质 体重可能会增强动机行为。此外，吸烟者倾向于食用高热量的饮食和 尼古丁会抑制体重。因此，体重和饮食很可能是重要的环境因素。 可能改变尼古丁强化的因素，特别是在尼古丁减少政策的背景下。在……里面 在人类和大鼠群体中，长期食用高热量饮食后体重增加存在差异 进入不同的人群：肥胖倾向(OP)和肥胖抵抗(OR)。利用选育的OP和 或者大鼠能够区分先前存在的潜在遗传因素的影响和 遗传和环境因素的结合。将使用自我管理模式收集数据 在OP和OR大鼠体内植入静脉导管，并允许做出反应以获得 注入尼古丁。使用肥胖和瘦吸烟者的创新啮齿动物模型，这个应用程序开始 测试新的假设，即饮食和高脂肪饮食的肥胖倾向是重要因素 改变尼古丁的强化特性，这在低剂量尼古丁时特别相关。这个 拟议的项目旨在研究长期摄入高能量饮食后体重对以下方面的影响： 1)初级尼古丁强化；2)其他显著环境刺激对尼古丁的贡献 增援。实验的目的是验证抵抗饮食导致的肥胖的假设。 增加对尼古丁的主要强化特性的反应，线索维持的行为，以及 增强尼古丁的特性。1)允许雌性和雄性OP和OR大鼠 对注射不同剂量的尼古丁的反应，假设对肥胖的抵抗力将 降低获得稳定行为的阈值剂量。2)线索维持行为的能力 条件增强剂将在雄性和雌性OP和OR大鼠身上进行测试。这些结果将推广到 测试饮食和体重对尼古丁强大的强化增强特性的影响。这 拟议的项目将是第一个在人类肥胖模型中测试尼古丁自我给药的项目。总而言之， 这些研究可能会为减少吸烟和总体烟草使用的战略提供洞察力 风险的特定亚群。

PROJECT SUMMARY The Food and Drug Administration (FDA) was recently granted the authority to regulate the content of nicotine in cigarettes to a “non-addictive” level; such a reduction could drastically reduce the number of smokers in the United States and improve public health. The smoking population is heterogeneous and it is likely that a subset of smokers will be less responsive to a reduction of nicotine content in cigarettes. Evidence suggests that consumption of densely caloric diets (i.e., foods high in fat or sugar content) and elevated body weight may enhance motivated behaviors. Further, smokers tend to consume densely caloric diets and nicotine suppresses body weight. Therefore, it is likely that body weight and diet are important environmental factors that could modify nicotine reinforcement, particularly in the context of nicotine reduction policy. In human and rat populations, body weight gain diverges after prolonged consumption of a densely caloric diet into distinct populations: obesity-prone (OP) and obesity-resistant (OR). Utilization of selectively bred OP and OR rats allow for the ability distinguish the impact of pre-existing underlying genetic factors from the combination of genetic and environmental factors. Data will be collected using a self-administration paradigm in which OP and OR rats are implanted with intravenous catheters and allowed to make responses to earn infusions of nicotine. Using an innovative rodent model of obese and lean smokers, this application begins to test the novel hypothesis that diet and propensity to develop obesity on a high fat diet are important factors modifying the reinforcing properties of nicotine, which are particularly relevant at low doses of nicotine. The proposed project aims to examine the effect of body weight after prolonged exposure to a high energy diet on: 1) primary nicotine reinforcement; and 2) the contribution of other salient environmental stimuli in nicotine reinforcement. Experiments are designed to test the hypothesis that resistance to develop diet-induced obesity increases responding for the primary reinforcing properties of nicotine, cue-maintained behavior, and the reinforcement enhancing properties of nicotine. 1) Female and male OP and OR rats will be allowed to respond for infusions of nicotine across a range of doses, with the hypothesis that resistance to obesity will decrease the threshold dose for acquisition of stable behavior. 2) The ability of cues to maintain behavior as conditioned reinforcers will be tested in male and female OP and OR rats. These results will be extended to test the impact of diet and body weight on nicotine’s powerful reinforcement enhancing properties. This proposed project will be the first to test nicotine self-administration in a model of human obesity. Collectively, these studies may provide insight regarding strategies for reducing smoking and overall tobacco use in a specific subpopulation of risk.