Synaptic Correlates of Ethanol-Mediated Anxiolysis

乙醇介导的抗焦虑作用的突触相关性

基本信息

项目摘要

DESCRIPTION (provided by applicant): There is a growing body of evidence suggesting that ethanol is used and abused for both its positive and negative reinforcing effects and that ethanol-mediated anxiolysis represents an important element of the negative reinforcement associated with ethanol drinking. Moreover, recent studies have suggested that ethanol's negative reinforcing effects gain salience with repeated ethanol exposure and withdrawal and may play an integral role in the development of, and relapse to, abusive drinking. Although much is known about the neurophysiological mechanisms responsible for the positive reinforcement associated with ethanol consumption, less is known about the neurocircuitry that contributes to many of ethanol's negative reinforcing effects. The overarching goal of this proposal is to integrate electrophysiological and behavioral approaches to begin to examine some of the neurophysiological mechanisms that may contribute to ethanol's anxiolytic effects. Specifically, these experiments will integrate electrophysiological and behavioral approaches to begin to address the central hypothesis that ethanol potentiation of GABAergic inhibition in the basolateral nucleus of the amygdala (BLA) contributes to specific measures of ethanol-mediated anxiolysis. Preliminary and published data suggest that there are two main GABAergic circuits within the BLA that mediate paracapsular, feedforward- and local, feedback-inhibition onto the principal output cells of this nucleus. Aims 1 and 2 will test the working hypothesis that ethanol potentiates both circuits, albeit via distinct mechanisms. We also plan to take advantage of a genetically engineered mouse line with increased sensitivity to some acute anxiolytic effects of ethanol. By combining behavioral and ex vivo electrophysiological studies in these genetically engineered mice (Aim 3) and outbred rats (Aim 4), we will test the working hypothesis that there is a positive relationship between ethanol potentiation of local and/or paracapsular GABAergic inhibition in the BLA and specific measures of ethanol-mediated anxiolysis. Collectively, these studies will identify the mechanisms that mediate and regulate ethanol potentiation of local and paracapsular GABAergic inhibition in the BLA and provide initial insight into some of the synaptic mechanisms that may contribute to ethanol's anxiolytic effects. PUBLIC HEALTH RELEVANCE: The first two aims of this proposal seek to determine how ethanol enhances two distinct inhibitory circuits in the basolateral amygdala (BLA), a brain region that has long been thought to play an integral role in the regulation of anxiety-like behaviors. Aims 3 and 4 outline a novel strategy that integrates behavioral and electrophysiological approaches to begin to assess the relationship between ethanol potentiation of BLA GABAergic inhibition and measures of ethanol-mediated anxiolysis. The results of these studies may lead to a better understanding of some of the neurobiological mechanisms that contribute to ethanol's anxiolytic effects and potentially reveal novel synaptic elements that can be targeted for the development of more effective treatments for alcoholism.
描述(由申请人提供):越来越多的证据表明,乙醇的使用和滥用既有积极的强化作用,也有消极的强化作用,乙醇介导的焦虑缓解是与酒精饮酒相关的消极强化的一个重要因素。此外,最近的研究表明,乙醇的负强化效应随着反复接触乙醇和戒断而变得突出,并可能在滥用饮酒的发展和复发中发挥不可或缺的作用。尽管我们对与乙醇消耗相关的正强化作用的神经生理机制了解甚多,但对导致许多乙醇负强化作用的神经回路了解甚少。本提案的首要目标是整合电生理和行为方法,开始研究一些可能有助于乙醇抗焦虑作用的神经生理机制。具体来说,这些实验将结合电生理和行为方法,开始解决核心假设,即乙醇增强杏仁核基底外侧核(BLA) gaba能抑制有助于酒精介导的焦虑缓解的具体措施。初步和已发表的数据表明,在BLA内有两种主要的gaba能回路,它们介导对该核主要输出细胞的囊旁前馈和局部反馈抑制。目标1和目标2将测试乙醇增强这两个回路的假设,尽管是通过不同的机制。我们还计划利用一种基因工程小鼠系,使其对乙醇的某些急性抗焦虑作用更加敏感。通过结合这些基因工程小鼠(Aim 3)和远交种大鼠(Aim 4)的行为和离体电生理研究,我们将验证乙醇增强BLA局部和/或包膜gaba能抑制与乙醇介导的焦虑缓解的具体措施之间存在正相关的工作假设。总的来说,这些研究将确定介导和调节乙醇增强BLA局部和囊旁gaba能抑制的机制,并初步了解一些可能有助于乙醇抗焦虑作用的突触机制。公共卫生相关性:该提案的前两个目的是试图确定乙醇如何增强基底外侧杏仁核(BLA)中的两个不同的抑制回路,这是一个长期以来被认为在调节焦虑样行为中起着不可或缺作用的大脑区域。目的3和4概述了一种整合行为和电生理方法的新策略,开始评估乙醇增强BLA - gaba能抑制与乙醇介导的焦虑缓解之间的关系。这些研究的结果可能会导致更好地理解一些神经生物学机制,这些机制有助于乙醇的抗焦虑作用,并可能揭示新的突触元件,这些元件可以作为开发更有效的酒精中毒治疗的目标。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

JEFFREY L WEINER其他文献

JEFFREY L WEINER的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('JEFFREY L WEINER', 18)}}的其他基金

Administrative Core
行政核心
  • 批准号:
    10526641
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Project 4: Adolescent Social Isolation Increases Vulnerability to the Behavioral and Neurobiological Consequences of Chronic Ethanol Exposure in Male and Female Rats
项目 4:青少年社会孤立增加了雄性和雌性大鼠对慢性乙醇暴露的行为和神经生物学后果的脆弱性
  • 批准号:
    10310704
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Project 4: Convergent behavioral and neurobiological adaptations promoted by rodent models of vulnerability to alcohol use disorder and post-traumatic stress disorder
项目 4:易患酒精使用障碍和创伤后应激障碍的啮齿动物模型促进趋同的行为和神经生物学适应
  • 批准号:
    10526646
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Wake Forest Translational Alcohol Research Center (WF-TARC)
维克森林转化酒精研究中心 (WF-TARC)
  • 批准号:
    10526640
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10310698
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Neural Substrates of Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder
共病酒精使用障碍和创伤后应激障碍的神经基质
  • 批准号:
    10188342
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Wake Forest Translational Alcohol Research Center (WF-TARC)
维克森林转化酒精研究中心 (WF-TARC)
  • 批准号:
    10310693
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Wake Forest Translational Alcohol Research Center (WF-TARC)
维克森林转化酒精研究中心 (WF-TARC)
  • 批准号:
    10079833
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
Neural Substrates of Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder
共病酒精使用障碍和创伤后应激障碍的神经基质
  • 批准号:
    9486289
  • 财政年份:
    2017
  • 资助金额:
    $ 35.15万
  • 项目类别:
2016 and 2018 Alcohol and the Nervous System GRC
2016 和 2018 酒精与神经系统 GRC
  • 批准号:
    9171365
  • 财政年份:
    2015
  • 资助金额:
    $ 35.15万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.15万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了