Nicotine dependence and central adiposity signaling

尼古丁依赖和中枢肥胖信号传导

基本信息

批准号：
7842594
负责人：
Adriaan Willem Bruijnzeel
金额：
$ 7.33万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2012-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Tobacco smoking is used to control food intake and body weight gain. Conversely, tobacco smoking cessation has been associated with increased food intake and accelerated body weight gain. Evidence indicates that smoking helps to control food intake by elevating adiposity signals (e.g., insulin and leptin) that modulate neurobehavioral processes. We hypothesize that chronic administration of nicotine results in adaptations in adiposty signaling in brain areas involved in food motivation. Upon cessation of nicotine administration these adaptations remain unopposed which leads to increased food intake. The first specific aim examines the effects of chronic nicotine administration on insulin and leptin signaling in two brain areas involved in food motivation, the arcuate hypothalamic nucleus and the ventral tegmental area. The intracranial self-stimulation procedure (ICSS) will be used to assess the effects of nicotine on adiposity signaling as it provides a quantitative measure of the motivational effects of changes in central adiposity signaling. Administration of insulin and leptin elevates brain reward thresholds, which is indicative of a decreased sensitivity to the electrical stimuli. It is expected that the threshold elevating effects of insulin and leptin are reduced during and after chronic exposure to nicotine. In addition, it is expected that plasma insulin and leptin levels are elevated during nicotine administration and return to baseline levels after cessation of nicotine administration. This pattern of results would suggest that that a decreased central responsivity to insulin or leptin mediates the increased food motivation associated with smoking cessation. Overweight adolescents are more likely to initiate tobacco smoking and develop a nicotine dependency than non-overweight adolescents. We hypothesize that the hormonal changes and neuroadaptations associated with diet-induced obesity potentiate the rewarding effects of nicotine and thereby accelerate the transition from experimenting with cigarettes to habitual smoking. Specific aim 2 examines the effects of diet-induced obesity on the rewarding effects of nicotine using the rat ICSS paradigm. Taken together, these proposed studies will start exploring the interplay between adiposity signaling and the rewarding effects of nicotine. Quitting smoking increases food intake and body weight gain. The studies described in this grant application investigate why quitting smoking leads to increased food intake and body weight gain. A better understanding of the brain mechanisms underlying post-cessation weight gain may contribute to new treatments for post-cessation weight gain and thereby improve smoking cessation rates.

描述（由申请人提供）：烟草吸烟用于控制食物摄入和体重增加。相反，烟草戒烟与食物摄入量增加和体重增加有关。证据表明，吸烟通过升高调节神经行为过程的肥胖信号（例如胰岛素和瘦素）来帮助控制食物摄入量。我们假设尼古丁长期给药会导致涉及食物动机的大脑区域的脂肪信号传导的适应。停止尼古丁给药后，这些适应仍未反对，从而导致食物摄入量增加。第一个特定目的研究了慢性尼古丁给药对涉及食物动机的两个大脑区域胰岛素和瘦素信号传导的影响，弧形下丘脑核和腹侧段落区域。颅内自刺激程序（ICS）将用于评估尼古丁对脂肪信号传导的影响，因为它提供了对中央肥胖信号变化的动机效应的定量度量。胰岛素和瘦素的给药可提高脑奖励阈值，这表明对电刺激的敏感性降低。预计在长期暴露于尼古丁期间和之后，胰岛素和瘦素的阈值升高作用会降低。此外，预计在尼古丁给药期间血浆胰岛素和瘦素水平升高，并在尼古丁施用后恢复到基线水平。这种结果模式表明，对胰岛素或瘦素的核心反应降低会介导与戒烟有关的食物动机增加。超重青少年比非过量青少年更有可能引发烟草吸烟并发展尼古丁依赖性。我们假设与饮食诱导的肥胖相关的激素变化和神经适应性增强了尼古丁的有益作用，从而加速了从实验卷烟到习惯吸烟的过渡。具体目标2使用大鼠ICSS范式检查了饮食引起的肥胖对尼古丁的奖励作用的影响。综上所述，这些提出的研究将开始探索肥胖信号传导与尼古丁的奖励作用之间的相互作用。戒烟会增加食物摄入量和体重增加。该赠款应用中描述的研究调查了为什么戒烟会导致食物摄入量增加和体重增加。更好地了解调子后体重增加后的大脑机制可能有助于新的治疗后，从而提高了戒烟率。