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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.

项目总结/文摘