A critical role for rapid estrogen signaling in alcohol addiction and anxiety

快速雌激素信号在酒精成瘾和焦虑中的关键作用

基本信息

批准号：
10447201
负责人：
Kristen Elizabeth Pleil
金额：
$ 44.04万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-10 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10447201
关键词：
Acute Adopted Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcohols Amygdaloid structure Anatomy Anxiety Anxiety Disorders Automobile Driving Behavior Behavior Control Behavioral Behavioral Mechanisms Biological Availability Biosensor Brain Calcium Cell Nucleus Cells Corticotropin-Releasing Hormone Data Disease Dose Drug usage Electrophysiology (science)Estradiol Estrogen Receptors Estrogens Estrus Experimental Designs Female Fiber Glutamates Gonadal Steroid Hormones Hormones Image In Situ Hybridization Interneuron function Lasers Lead Mass Spectrum Analysis Measures Membrane Menstrual cycle Neurons Neuropeptides Optics Output Periodicity Peripheral Pharmacology Phenotype Photometry Play Population Prevention RNA Interference Recording of previous events Research Resolution Risk Risk Factors Role Signal Transduction Slice Source Stress Structure of terminal stria nuclei of preoptic region Synapses Technology Time Woman Work addiction alcohol comorbidity alcohol exposure alcohol use disorder binge drinking drinking drinking behavior experimental study in vivo male men negative affect neural circuit neurophysiology neuropsychiatric disorder novel novel therapeutic intervention optogenetics receptor receptor binding recruit relating to nervous system reproductive response sensor sex stress reactivity stressor synaptic function tool transmission process

项目摘要

Project Summary/Abstract Binge alcohol drinking and high stress reactivity are leading risk factors for anxiety and alcohol use disorders, and women are at twice the risk for co-expression of these diseases. The sex hormone estrogen has been implicated in playing a modulatory role in anxiety and alcohol/drug use and may be related to the telescoping of addiction observed in women by amplifying the positive and negative components of binge alcohol consumption and withdrawal. Further, alcohol consumption itself may be able to stimulate estrogen synthesis to promote drinking behavior, suggesting that estrogen signaling may be an important mechanism in addiction for both males and females. However, the mechanisms by which estrogen regulates neuronal function to control these behaviors is unknown. We hypothesize that estrogen signals at membrane-bound receptors located at discrete synaptic nodes of limbic circuitry to modulate their control of behavior, and that this mechanism is prominent at baseline in females but becomes more important in males across alcohol drinking exposure. In the proposed work, we examine the locus and mechanism of endogenous estrogen signaling, its effect on circuit function and corresponding behavior, and alcohol-induced plasticity in estrogen modulation in both males and females.

项目摘要/摘要暴饮暴食和高压力反应性是焦虑和酒精使用障碍的主要危险因素，妇女的共同表达风险是这些疾病的两倍。性激素雌激素已经与在焦虑和酒精/药物使用中发挥调节作用有关，可能与望远镜有关在女性中观察到的成瘾是通过扩增暴饮暴食的正和负分量消费和退出。此外，饮酒本身可能能够刺激雌激素合成为了促进饮酒行为，表明雌激素信号传导可能是成瘾的重要机制对于男性和女性。但是，雌激素调节神经元功能的机制控制这些行为是未知的。我们假设在膜结合受体处的雌激素信号位于边缘电路的离散突触节点以调节其行为的控制，这是在女性的基线时，机制很突出，但在饮酒中的男性中变得越来越重要接触。在拟议的工作中，我们检查了内源性雌激素信号传导的基因座和机制对电路功能和相应行为的影响，以及酒精诱导的雌激素调节中的可塑性男性和女性。