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 可归因于酒精、尼古丁和其他毒品的因素是不可估量的。这个 对药物神经生物学底物感兴趣的研究人员的目标 滥用是为了理解强势的动机和上瘾的特性 药物，并开发更好的治疗醉酒，渴求，和 旧病复发。近年来，在第一部分方面取得了很大进展。 这一目标。调控补肾益气作用的神经通路 药物是众所周知的，最近取得了令人瞩目的进展 了解药物对分子机制和基因的影响 表情。这项建议的目的是详细研究基本的 伏隔核的行为功能，整合行为， 药理学和分子方法。伏隔核，位于 在腹内侧纹状体内，是药物的重要神经底物 增援。因此，人们认为，既然药物似乎能发挥作用 它们在这个区域及其相关电路中的有益性质， 伏隔可能在生物强化和 对食欲行为的调节。然而，人们对此知之甚少， 关于作为其功能基础的特定神经分子机制 伏尔本家族。这个项目的目的是调查 最近指定的“核心”和“外壳”分区域的职能 伏隔核。具体地说，我们将1)调查 多巴胺能和谷氨酸能受体机制及其相关 伏隔核内反应强化的细胞内机制 学习，以及2)我们将研究涉及的发射机机制和电路 在控制伏隔虫壳内的取食行为方面。 可利用的技术包括局部微量注射特定化合物 受体的行为和细胞内的转导机制，在 结合行为分析和转录测量 可能在学习或学习中发挥作用的因子和磷酸化酶 动机行为。进一步了解系统的基本知识和 药物作用的底物，这可能会导致 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.