ALCOHOL REGULATION OF KAPPA OPIOID RECEPTOR SYSTEMS IN THE EXTENDED AMYGDALA

扩展杏仁核中 KAPPA 阿片受体系统的酒精调节

基本信息

批准号：
8684994
负责人：
Nicole Ashley Crowley
金额：
$ 3.19万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8684994
关键词：
Affect Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Amygdaloid structure Anxiety Anxiety Disorders Behavior Behavioral Brain Brain region Cell Nucleus Chronic Comorbidity Data Development Dynorphins Electrophysiology (science)Emotional Environment Ethanol Future Glutamates Goals Individual Intervention Investigation Ligands Mediating Methods Modeling Molecular Neurons Neurotransmitters Opioid Opioid Receptor Pathway interactions Play Public Health Receptor Activation Regulation Research Role Signal Transduction Slice Stress Stressful Event Structure of terminal stria nuclei of preoptic region Synapses System Testing Therapeutic Time Training Work alcohol abuse therapy alcohol exposure alcohol use disorder alcoholism therapy behavior influence drinking behavior experience innovation mouse model neurobiological mechanism neuronal circuitry neurophysiology optogenetics public health relevance receptor receptor function response transmission process

项目摘要

DESCRIPTION (provided by applicant): Alcohol use disorders represent a major public health problem, and to date, no comprehensive treatment or intervention is available. The Bed Nucleus of the Stria Terminalis (BNST) is involved in integrating cortical and subcortical inputs to orchestrate behavioral responses, and has been implicated in alcohol use and abuse, as well as stress related behaviors. The kappa opioid receptor (KOR) has been demonstrated in the BNST to alter neurotransmitter signaling [1], though its effect on glutamatergic transmission has yet to be elucidated. The goals of this project are to conduct a thorough investigation and characterization into the role of KORs on glutamatergic signaling in the BNST, and how this connection is altered by a model of alcohol dependence. To complete the first aim, I will use slice electrophysiology to evaluate the function, signaling, and locus of glutamatergic KORs in the BNST. To complete this second aim, I will use a combination of optogenetics, chronic-intermittent ethanol exposure, and slice electrophysiology to assess how KORs modulate pathways- specific inputs to the BNST both before and after ethanol exposure. Thus, this proposal will use a combination of innovative approaches to provide thorough and convergent evidence characterizing KOR modulation of glutamatergic transmission in the BNST.

描述（由申请人提供）：酒精使用障碍是一个主要的公共卫生问题，迄今为止，尚无可用的综合治疗或干预措施。终纹床核 (BNST) 参与整合皮质和皮质下输入以协调行为反应，并与酒精使用和滥用以及压力相关行为有关。 kappa 阿片受体 (KOR) 已在 BNST 中被证明可以改变神经递质信号传导 [1]，但其对谷氨酸能传递的影响尚未确定予以阐明。该项目的目标是对 KOR 对 BNST 中谷氨酸信号传导的作用进行彻底的调查和表征，以及酒精依赖模型如何改变这种联系。为了完成第一个目标，我将使用切片电生理学来评估 BNST 中谷氨酸能 KOR 的功能、信号传导和位点。为了完成第二个目标，我将结合使用光遗传学、慢性间歇性乙醇暴露和切片电生理学来评估 KOR 如何在乙醇暴露之前和之后调节 BNST 的通路特异性输入。因此，该提案将结合使用创新方法来提供全面且一致的证据，以表征 BNST 中谷氨酸传输的 KOR 调节。