5/8 INIA Stress and Chronic Alcohol Interactions: Probing brain circuits that regulate alcohol stress interactions

5/8 INIA 压力和慢性酒精相互作用：探索调节酒精压力相互作用的大脑回路

• 批准号: 10574573
• 负责人: Thomas L. Kash
• 金额: $ 44.87万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-10 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574573
• 关键词: Address; Adrenergic Receptor; Affect; Affective; Agonist; Alcohol consumption; Alcohol dependence; Alcohols; Amygdaloid structure; Anabolism; Anatomy; Area; Behavior; Behavior assessment; Biosensor; Brain; Brain imaging; Brain region; CRISPR/Cas technology; Chronic; Collaborations; Consumption; Coping Behavior; Coupled; Disease; Dopamine; Dynorphins; Electrophysiology (science); Evaluation; Exposure to; Female; Fiber; Functional Magnetic Resonance Imaging; Funding; Glutamates; Goals; Grant; Heavy Drinking; Individual; Investigation; Knock-out; Laboratory Finding; Modality; Modeling; Molecular; Mus; Neurons; Norepinephrine; Outcome; Outcome Measure; Output; Pathway Analysis; Persons; Photometry; Physiology; Play; Prevalence; Property; Receptor Signaling; Regulation; Research Project Grants; Role; Sex Differences; Signal Pathway; Signal Transduction; Slice; Stress; Stress and Coping; Structure; Structure of terminal stria nuclei of preoptic region; System; Testing; United States; Ventral Tegmental Area; Withdrawal; Work; activity marker; alcohol exposure; alcohol response; alcohol use disorder; anxiety-like behavior; gamma-Aminobutyric Acid; genetic manipulation; in vivo; individual variation; insight; kappa opioid receptors; male; multidrug abuse; negative affect; neurobiological mechanism; neuroregulation; nonhuman primate; noradrenergic; norepinephrine system; novel; pharmacologic; response

Project Summary In this project we will mechanistically explore two neuromodulatory systems within the extended amydala and how they regulate plasticity and behavior following alcohol exposure and stress. In particular, in aims 1 and 2 we will utilize novel CRISPR technology to manipulate signaling in discrete brain regions, building on our prior investigations. In aim 1, we will explore the role of central amygdala (CeA) Kappa Opioid Receptor (KOR) signaling in alcohol and stress driven alterations in plasticity and in vivo dynamics of specific bed nucleus of the stria terminalis (BNST) outputs. In aim 2, we will investigate the contribution of noradrenergic signaling to alcohol drinking and alcohol driven disruptions of behavior. In aim 3, we will collaborate within and across INIA consortia in three ways (i.) investigating how CeA KOR knock out regulates alcohol exposure induced disruptions of dopamine signaling in vivo (Jones/Holleran component) , (ii.) investigating adrenergic receptor modulation in the BNST following alcohol consumption (Grant/Schnitko), (iii.) whole brain cFos analysis following GPR88 agonism to reduce alcohol consumption (Kieffer/Harsan). Thus, these integrated, yet independent aims, will provide circuit specific mechanistic findings in critical nodes that have been established to contribute to multiple aspects of the positive and negative reinforcing properties of alcohol.

项目摘要 在这个项目中，我们将机械地探索扩展的 杏仁核以及它们如何调节酒精暴露和压力后的可塑性和行为。在……里面 具体地说，在目标1和目标2中，我们将使用新的CRISPR技术来处理离散的信号 大脑区域，建立在我们之前的研究基础上。在目标1中，我们将探索中央杏仁核的作用。 (CEA)Kappa阿片受体(KOR)信号在酒精和应激引起的可塑性和 终纹特定床核(BNST)输出的活体动力学。在目标2中，我们将调查 去甲肾上腺素能信号在饮酒和酒精引起的脑电活动中断中的作用 行为。在目标3中，我们将在INIA财团内部和之间通过三种方式进行合作(即：)调查 CEA-KOR基因敲除对酒精暴露所致体内多巴胺信号转导的影响 (琼斯/霍勒兰部分)，(二)BNST后肾上腺素能受体调节的研究 酒精消费(Grant/Schnitko)，(iii.)GPR88激动剂作用后的全脑CFOS分析 减少酒精消费(基弗/哈桑)。因此，这些综合而又独立的目标将提供 已建立的关键节点中特定于电路的机制发现 酒精的正负增强特性的各个方面。