OPIOID SYSTEMS IN VENTRAL STRIATUM AND FOOD REWARD

描述：(改编自申请人的摘要) 美国公共卫生面临的两个最大威胁 进入下个世纪的是吸毒和肥胖。每年死亡人数 仅尼古丁和酒精依赖一项就估计有 45万。此外，卫生局局长指出..“吸烟后， 与体重相关的疾病是老年人死亡的第二大原因。 每年在美国造成约30万人丧生…… 个人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看起来没有亲缘关系，他们有共同的 重要的共性。奖励药物对神经回路的影响 被认为在成瘾过程中发生了深刻变化的是那些 它控制着我们最重要的自然奖励--食物的摄取。神经学 最明显的与吸毒成瘾有关的系统 腹侧纹状体(包括伏隔核)及其相关 回路，一个也从属于动机行为的区域，例如 进食、饮水、性行为和激励性学习。为了 开发成功的治疗成瘾和饮食失调的方法，这是 需要进一步了解潜在的生物学机制 动力。具体地说，详细调查将是有用的 饮食享乐方面的神经机制(“食物” 这里提出的研究将解决这个问题， 将行为学、药理学、解剖学和分子学相结合 生物学(原位杂交)技术。主要的假设是 指导拟议的实验的是阿片系统，特别是在 腹侧纹状体在动物的情感活动中起着至关重要的作用 对食物的反应；这是在“喜欢”的过程中，或在味觉 从非常美味的食物中获得的快乐。还进一步提出了 腹侧纹状体是大脑的关键区域 代谢神经体液信号与中枢控制整合在一起。 动机状态和适应性反应。在这些实验中，我们 将分析脑啡肽基因在信号转导通路中的作用 阿片介导性喂养中胰岛素的表达和循环 还要检查可能涉及的底层电路的组织 在处理适口性信号方面。

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.