Nicotine dependence and central adiposity signaling

尼古丁依赖和中枢肥胖信号传导

• 批准号: 7529382
• 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
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7529382
• 关键词: Adolescent; Aftercare; Applications Grants; Area; Brain; Cell Nucleus; Child; Chronic; Chronic Disease; Cigarette; Dependency; Development; Diet; Disease; Eating; Electrodes; Exposure to; Fatty acid glycerol esters; Food; Homeostasis; Hormonal Change; Hypothalamic structure; Incentives; Insulin; Lateral; Left; Leptin; Measures; Mediating; Motivation; Neurons; Nicotine; Nicotine Dependence; Obesity; Overweight; Pattern; Pharmacological Treatment; Physical activity; Plasma; Prevalence; Procedures; Process; Rattus; Relapse; Rewards; Risk Factors; Saline; Self Stimulation; Signal Transduction; Site; Smoke; Smoking; Stimulus; Tobacco; Tobacco smoking; United States; Ventral Tegmental Area; Weight Gain; Work; base; improved; innovation; median forebrain bundle; mortality; neuroadaptation; neurobehavioral; research study; smoking cessation

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(申请人提供)：吸烟用于控制食物摄入量和体重增加。相反，戒烟与增加食物摄入量和加速体重增加有关。有证据表明，吸烟通过提高调节神经行为过程的肥胖信号(如胰岛素和瘦素)来帮助控制食物摄入量。我们假设，长期服用尼古丁会导致与食物动机相关的大脑区域脂肪信号的适应。停止服用尼古丁后，这些适应保持不变，从而导致食物摄入量增加。第一个具体目的是研究长期服用尼古丁对与食物动机有关的两个大脑区域--下丘脑弓状核和腹侧被盖区--胰岛素和瘦素信号的影响。颅内自我刺激程序(ICSS)将被用来评估尼古丁对肥胖信号的影响，因为它提供了对中枢肥胖信号变化的激励效应的定量测量。注射胰岛素和瘦素会提高大脑的奖励阈值，这表明对电刺激的敏感度降低。预计在长期接触尼古丁期间和之后，胰岛素和瘦素的阈值升高效应会减弱。此外，预计血浆胰岛素和瘦素水平在尼古丁给药期间会升高，并在停止尼古丁给药后恢复到基线水平。这一结果模式将表明，对胰岛素或瘦素的中枢反应性降低介导了与戒烟相关的食物动机的增加。超重的青少年比非超重的青少年更有可能开始吸烟并对尼古丁产生依赖。我们假设，与饮食诱导的肥胖相关的荷尔蒙变化和神经适应增强了尼古丁的奖励效应，从而加速了从尝试吸烟到习惯吸烟的转变。特定目的2使用大鼠ICSS范式检查饮食诱导的肥胖对尼古丁奖励效应的影响。综上所述，这些拟议的研究将开始探索肥胖信号和尼古丁回报效应之间的相互作用。戒烟会增加食物摄入量和体重增加。在这项拨款申请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。更好地了解戒烟后体重增加背后的大脑机制可能有助于为戒烟后体重增加提供新的治疗方法，从而提高戒烟率。