NEURAL MECHANISMS IN THE NUCLEUS ACCUMBENS AND BEHAVIOR

描述：（申请人摘要） 药物滥用是美国的主要健康问题。 成本 在死亡、疾病、伤害和精神痛苦方面对社会的影响 酒精，尼古丁和其他药物的作用是不可估量的。 的 对药物的神经生物学底物感兴趣的研究人员的目标 滥用是为了了解强大的动机和成瘾特性， 药物，并开发更好的治疗中毒，渴望， 复发 近年来，在第一部分方面取得了很大进展 这个目标。 控制强化效应的神经通路 药物是众所周知的，最近取得了显着的进展， 在了解药物对分子机制和基因的影响方面取得的成就 表情 本建议的目的是详细研究基本的 丘脑核的行为功能，整合行为， 药理学和分子方法。 脑桥核位于 在腹内侧纹状体内，是药物的重要神经基质 加固. 据推测，因此，由于药物似乎发挥 它们在这个区域及其相关电路中的有益特性， 生物强化可能在生物强化中发挥重要作用， 食欲行为的调节。 然而，我们所知甚少， 关于特定的神经分子机制， 一家人 这个项目的目的是调查行为 最近指定的“核心”和“外壳”次区域的职能 丘脑核 具体来说，我们将1）调查的作用 多巴胺能和多巴胺能受体机制及其相关的 反应强化的细胞内机制 学习，2）我们将研究发射机机制和电路参与 在控制进食行为中的作用。 所使用的技术包括特定化合物的局部微量输注 受体和细胞内转导机制作用， 结合行为分析和转录测量 因子和磷酸化酶，可能在学习或 动机行为 对系统的进一步基本了解， 药物作用的底物，这可能是由这一点引起的 研究，可以帮助开发更好的成瘾疗法。

DESCRIPTION: (Applicant's Abstract) Substance abuse is the major health problem in the United States. The cost to society in terms of death, disease, injury and emotional distress attributable to alcohol, nicotine, and other drugs is immeasurable. The goal of researchers interested in the neurobiological substrates of drug abuse is to understand the powerful motivating and addictive properties of drugs, and to develop better treatments for intoxication, craving, and relapse. In recent years, much progress has been made toward the first part of this goal. The neural pathways governing the reinforcing effects of drugs are well known, and very recently remarkable advances have been achieved in learning about effects of drugs on molecular mechanisms and gene expression. The objective of this proposal is to study in detail the basic behavioral functions of the nucleus accumbens, integrating behavioral, pharmacological and molecular approaches. The nucleus accumbens, located within the ventromedial striatum, is an important neural substrate for drug reinforcement. It is assumed, therefore, that since drugs appear to exert their rewarding properties in this region and its associated circuits, the accumbens may play a fundamental role in biological reinforcement and regulation of appetitive behaviors. Relatively little is known, however, about the specific neuromolecular mechanisms that underlie the functions of the accumbens. The aims of this project are to investigate the behavioral functions of the recently designated "core" and "shell" subregions of the nucleus accumbens. Specifically, we will 1) investigate the role of dopaminergic and glutamatergic receptor mechanisms and their associated intracellular mechanisms within the accumbens core in response-reinforcement learning, and 2) we will study transmitter mechanisms and circuitry involved in controlling feeding behavior located within the accumbens shell. Techniques to be utilized include local microinfusions of specific compounds that act of receptor and intracellular transduction mechanisms, in combination with behavioral analysis, and measurement of transcription factors and phosphorylating enzymes that may play a role in learning or motivated behavior. Further basic understanding of the systems and substrates upon which drugs act, which could potentially result from this research, could help to develop better addiction therapies.