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（由申请方提供）：吸烟用于控制食物摄入和体重增加。相反，戒烟与食物摄入量增加和体重增加加速有关。有证据表明，吸烟有助于通过提高肥胖信号（例如，胰岛素和瘦素）调节神经行为过程。我们推测，长期服用尼古丁会导致与食物动机有关的大脑区域的脂肪形成信号的适应。停止尼古丁给药后，这些适应性变化保持不变，导致食物摄入量增加。第一个具体的目的是研究长期尼古丁给药对胰岛素和瘦素信号在两个大脑区域参与食物动机，弓状下丘脑核和腹侧被盖区的影响。颅内自我刺激程序（ICSS）将用于评估尼古丁对肥胖信号传导的影响，因为它提供了中枢肥胖信号传导变化的激励效应的定量测量。胰岛素和瘦素的施用提高了大脑奖励阈值，这表明对电刺激的敏感性降低。预期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效应降低。此外，预计尼古丁给药期间血浆胰岛素和瘦素水平升高，停止尼古丁给药后恢复至基线水平。这种结果模式表明，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增加。超重青少年比非超重青少年更容易开始吸烟并产生尼古丁依赖。我们推测，与饮食诱导的肥胖相关的激素变化和神经适应增强了尼古丁的奖励作用，从而加速了从尝试吸烟到习惯性吸烟的转变。具体目标2使用大鼠ICSS范例检查饮食诱导的肥胖对尼古丁的奖励作用的影响。总之，这些拟议的研究将开始探索肥胖信号与尼古丁的奖励效应之间的相互作用。戒烟会增加食物摄入量和体重增加。本研究报告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的大脑机制可能有助于戒烟后体重增加的新治疗方法，从而提高戒烟率。