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

• 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
• 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

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

项目摘要/摘要 酒精使用障碍(AUD)在我们国家和全世界都是一个日益严重的问题。新冠肺炎大流行已经 导致饮酒显著增加，其中女性的增加尤为明显，许多人 由于与禁欲相关的负面情感状态而导致的复发。的功能连接网络 为了更好地帮助人们，需要禁欲引发的负面情绪来充分理解这些状态 饱受澳元之苦。我们实验室之前的工作已经阐明了部分途径，描绘了一个岛到 酒精戒断过程中激活的BNST通路通过检测男性和 女性，通过基于运动的行为分析。然而，由于最近文献中的发现，它是 这些以运动为基础的分析可能没有揭示出儿童消极情感行为的全部范围 雌性老鼠。申请者Amanda Salazar建议在家长资助的基础上进行实验，以 测试未在我们的CDFA模型中测试的非基于运动的行为分析，因此是 父授权的逻辑扩展。这将使我们能够正确地识别负面情绪中的性别差异 在戒酒期间的小鼠身上。我们假设雌性老鼠会表现出更强烈的酒精含量 惊吓反应试验(声学、呼气、足部电击)中戒酒诱导的负性情感样表型 与雄鼠相比。阿曼达将在分子生物学背景的基础上获得有意义的培训 在酒精模型、立体定向手术、纤维光度测量以及统计分析和数据呈现方面。 导师制还将侧重于进一步提高科学沟通技能，并在 实验室、项目和社区，以实现她进入博士项目的目标