Delineating sex-specific abstinence-induced negative affective behavior in insular circuitry

描绘岛回路中特定性别禁欲引起的负面情感行为

基本信息

批准号：
10732894
负责人：
Samuel William Centanni
金额：
$ 4.87万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-28 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10732894
关键词：
Abstinence Acoustics Affective Air Alcohol consumption Alcohols Animal Behavior Anxiety Anxiety Disorders Area Behavior Behavior assessment Behavioral Assay Behavioral Model Biological Assay COVID-19 pandemic Communication Communities Cues Data Doctor of Philosophy Exhibits Female Fiber Freezing Funding Genetic Engineering Goals Grant Human Individual Insula of Reil Interoception Journals Literature Machine Learning Measures Mediating Mental Depression Mental disorders Mentorship Modeling Molecular Biology Mood Disorders Mus Neurons Operative Surgical Procedures Paper Pathway interactions Pattern Persons Phenotype Photometry Play Prevalence Proxy Relapse Rodent Rodent Model Role Sensory Sex Differences Shock Signal Transduction Somatosensory Cortex Startle Reaction Statistical Data Interpretation Stimulus Stress Structure of terminal stria nuclei of preoptic region Techniques Testing Thalamic structure Training United States Woman Work alcohol abstinence alcohol use disorder calcium indicator career development comorbidity experimental study foot in vivo interest male meetings men mouse model negative affect neural outreach parent grant programs response responsible research conduct sex skills success

项目摘要

Project Summary/Abstract Alcohol Use Disorder (AUD) is a growing problem in our nation and worldwide. The COVID-19 pandemic has led to a significant increase in alcohol use, with a particularly sharp rise in women, with many people relapsing due to the negative affective states correlated with abstinence. A functional connectivity network of abstinence-induced negative affect is needed to fully understand these states in order to better help people suffering with AUD. Previous work in our lab has elucidated parts of the pathway, delineating an insula to BNST pathway that is activated during alcohol abstinence induced negative affect by testing male and female though locomotor based behavioral assays. Due to findings in recent literature, however, it is possible that these locomotor-based assays do not reveal the full scope of negative affective behavior in female mice. The applicant, Amanda Salazar, proposes to build on the experiments in the parent grant to test a non-locomotor based behavioral assay that has not been tested in our CDFA model, and is therefore a logical extension of the parent grant. This will allow us to properly identify sex differences in negative affect in mice during alcohol abstinence. We hypothesize that female mice will exhibit a much stronger alcohol abstinence-induced negative affect-like phenotype in startle response tests (acoustic, air puff, foot shock) compared to male mice. Amanda will build off her molecular biology background to gain meaningful training in alcohol models, stereotaxic surgery, fiber photometry, and statistical analysis and presentation of data. Mentorship will also focus on furthering scientific communication skills and engaging in outreach within the lab, the program, and the community to reach her goal of admittance into a PhD program

项目概要/摘要酒精使用障碍（AUD）是我们国家和全世界日益严重的问题。 COVID-19 大流行已导致饮酒量显着增加，尤其是女性的急剧增加，许多人由于与禁欲相关的负面情感状态而复发。功能连接网络需要禁欲引起的负面影响来充分理解这些状态，以便更好地帮助人们受澳元困扰。我们实验室之前的工作已经阐明了该通路的部分内容，描绘了一个岛叶通过测试男性和女性，戒酒期间激活的 BNST 通路会诱发负面影响女性基于运动的行为测定。然而，根据最近文献的发现，这些基于运动的分析可能无法揭示消极情感行为的全部范围雌性小鼠。申请人阿曼达·萨拉查 (Amanda Salazar) 提议以家长资助中的实验为基础测试基于非运动的行为测定，该测定尚未在我们的 CDFA 模型中进行过测试，因此是一种父授权的逻辑扩展。这将使我们能够正确识别负面情绪中的性别差异在戒酒期间的小鼠中。我们假设雌性小鼠会表现出更强烈的酒精惊吓反应测试中禁欲引起的负面情感样表型（声音、喷气、足部震动）与雄性小鼠相比。阿曼达将利用她的分子生物学背景来获得有意义的培训酒精模型、立体定位手术、纤维光度测定以及数据的统计分析和呈现。指导还将侧重于提高科学沟通技巧并参与范围内的外展活动实验室、项目和社区，以实现她进入博士项目的目标