OPIOID SYSTEMS IN VENTRAL STRIATUM AND FOOD REWARD

腹侧纹状体中的阿片类药物系统和食物奖励

• 批准号: 6125018
• 负责人: Ann E. Kelley
• 金额: $ 15.63万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6125018
• 关键词: G protein; adenylate cyclase; behavioral /social science research tag; biological signal transduction; brain mapping; dietary lipid; dopamine receptor; drug addiction; eating; endogenous opioid; enkephalins; gene expression; glutamate receptor; in situ hybridization; insulin receptor; laboratory rat; motivation; neuroanatomy; neuropharmacology; neuroregulation; nucleus accumbens; nutrition related tag; psychopharmacology; reinforcer

DESCRIPTION: (Adapted From The Applicant's Abstract) Two of the greatest threats to public health in the United States as we enter the next century are drug addiction and obesity. Annual deaths attributable to nicotine and alcohol dependence alone are estimated at 450,000. Moreover, the surgeon general has noted that .." after smoking, weight related conditions are the second leading cause of death in the U.S. resulting in about 300,000 lives lost each year..." These individuals are at greatly elevated risk for many disorders, such as heart disease, hypertension, and diabetes. While these two health issues do not appear related in terms of etiology or phenomenology, they share important commonalities. The neural circuits affected by rewarding drugs and presumed to be profoundly altered in addiction are the very pathways that control intake of our most vital natural reward, food. The neural system most clearly implicated in drug addiction con stitutes the ventral striaturn (includin nucleus accumbens) and its associated circuitry, a region that also subserves motivated behaviors, such as feeding, drinking, sexual behavior, and incentive learning. In order to develop successful treatments for addiction and eating disorders, it is necessary to further understand the biological mechanisms underlying motivation. Specifically, it would be useful to investigate in detail the neural mecahnisms underlying the hedonic aspects of eating ("food reward"). The research proposed here will address this question, integrating behavioral, pharmacological, anatomical and molecular biological (in situ hybridization) techniques. The main hypothesis that guides the proposed experiments is that opioid systems, particularly in the ventral striaturn, play a critical role in an animal's affective response to food; that is in the "liking" process, or the orosensory pleasure derived from highly palatable foods. It is further proposed that the ventral striaturn is a key brain region where peripheral metabolic neurohumoral signals are integrated with central control of motivational states and adaptive responding. In these experiments, we will analyze the role of signal transduction pathways, enkephalin gene expression, and circulating insulin in opioid-mediated feeding, and will also examine organization of underlying circuitries that may be involved in processing of palatability signals.

描述：（改编自申请人的摘要） 我们面临的美国公共卫生面临的两个最大威胁 进入下个世纪的是毒瘾和肥胖。每年死亡人数 仅归因于尼古丁和酒精依赖的估计为 450,000。此外，卫生局局长指出……”吸烟后， 与体重相关的疾病是第二大死亡原因 美国每年造成约 30 万人丧生……”这些 个体患许多疾病的风险大大增加，例如 心脏病、高血压和糖尿病。虽然这两个健康问题 在病因学或现象学方面似乎没有相关性，但它们有共同点 重要的共同点。受奖励药物影响的神经回路 被认为在成瘾过程中发生深刻改变的是这些途径 控制我们最重要的自然奖励——食物的摄入量。神经元 与吸毒成瘾最明显相关的系统构成 腹侧纹状体（包括伏隔核）及其相关 电路，一个也促进动机行为的区域，例如 喂养、饮水、性行为和激励学习。为了 开发成功的治疗成瘾和饮食失调的方法 有必要进一步了解其潜在的生物学机制 动机。具体来说，详细调查是有用的 饮食享乐方面的神经机制（“食物 奖励”）。这里提出的研究将解决这个问题， 整合行为、药理学、解剖学和分子 生物（原位杂交）技术。主要假设是 指导拟议实验的是阿片类药物系统，特别是在 腹侧纹状体，在动物的情感中起着至关重要的作用 对食物的反应；那是在“喜欢”的过程中，或者说是嗅觉过程 来自美味食物的快乐。进一步提出 腹侧纹状体是大脑的一个关键区域 代谢神经体液信号与中枢控制相结合 动机状态和适应性反应。在这些实验中，我们 将分析信号转导途径、脑啡肽基因的作用 阿片类药物介导的喂养中的表达和循环胰岛素，并且将 还检查可能涉及的底层电路的组织 在适口性信号的处理中。