Noradrenergic Regulation in the BNST

BNST 中的去甲肾上腺素能调节

基本信息

批准号：
7917924
负责人：
DANNY G WINDER
金额：
$ 36.7万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7917924
关键词：
Acute Adrenergic Agonists Adrenergic Antagonists Adrenergic Receptor Agonist Amygdaloid structure Animals Behavior Behavioral Brain Brain region Cell Nucleus Cells Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Receptors Depressed mood Dopamine Dopamine Receptor Drug Addiction Drug usage Electron Microscopy Esthesia Funding Genetic Goals Health Intake Knockout Mice Ligands Literature Long-Term Depression Maps Mediating Molecular Neurons Norepinephrine Norepinephrine Receptors Pathway interactions Pharmaceutical Preparations Play Population Process Property Receptor Activation Regulation Reporting Rewards Role Signal Transduction Societies Stress Structure of terminal stria nuclei of preoptic region Synapses Synaptic Transmission System Testing Tetanus Helper Peptide Work addiction drug of abuse drug relapse drug seeking behavior human relapse in vivo insight interest mesolimbic system nerve supply noradrenergic novel preference public health relevance receptor research study response stressor therapeutic development transmission process

项目摘要

DESCRIPTION (provided by applicant): Addiction is a tremendous health and financial burden on our society. A growing literature indicates that norepinephrine in the brain plays a key role in stress-reward interactions that may mediate key behavioral responses to drugs of abuse. A previously unappreciated group of noradrenergic neurons in the field of addiction, cells that project through the ventral noradrenergic bundle (VNAB), are thought to supply the key norepinephrine. The primary target of the VNAB in the brain is a group of nuclei referred to as the extended amygdala. In the previous funding period, we identified actions of each of the major classes of noradrenergic receptors on excitatory synaptic transmission in the bed nucleus of the stria terminalis, a major component of the extended amygdala. Here, we propose experiments to assess molecular mechanisms involved in these actions, and to begin to place these actions in the context of microcircuitry within the extended amygdala. Further, we propose to examine whether overlapping populations of neurons in the extended amygdala are activated by drugs of abuse and stressors, and whether this activation is regulated by noradrenergic ligands. In total, the proposed work will begin to define specific mechanisms likely to play key roles in stress-induced reinstatement of drug seeking behavior, thus providing new potential opportunities for therapeutic development. PUBLIC HEALTH RELEVANCE: Addiction poses an enormous health and financial burden on our society. Currently, our understanding of the brain circuitries involved in addiction is far from complete. The successful completion of these proposed studies will result in important new information about neurons that may be involved in addiction, potentially creating new targets for therapeutics development.

描述（由申请人提供）：成瘾是我们社会的巨大健康和经济负担。越来越多的文献表明，大脑中的去甲肾上腺素在压力奖励相互作用中起着关键作用，这可能介导对滥用药物的关键行为反应。在成瘾领域，先前未经批准的甲肾上腺素能神经元，通过腹侧去甲肾上腺素能束（VNAB）投射的细胞被认为提供了关键的去甲肾上腺素。大脑中VNAB的主要靶标是一组核，称为扩展的杏仁核。在上一个资金期间，我们确定了甲肾上腺素能受体的每个主要类别的作用对延伸杏仁核的主要成分的质子底核中的兴奋性突触传播。在这里，我们提出了实验，以评估这些作用中涉及的分子机制，并开始在扩展的杏仁核中将这些作用放置在微电路的背景下。此外，我们建议检查扩展杏仁核中神经元的重叠种群是否被滥用和压力源的药物激活，以及这种激活是否受到去甲肾上腺素能配体的调节。总的来说，拟议的工作将开始定义可能在压力引起的恢复毒品行为中起关键作用的特定机制，从而为治疗性发育提供了新的潜在机会。公共卫生相关性：成瘾给我们的社会带来了巨大的健康和经济负担。当前，我们对成瘾涉及的脑电路的理解远非完整。这些提出的研究的成功完成将导致有关可能与成瘾有关的神经元的重要新信息，并有可能为治疗剂开发创造新的目标。