FMRP in the striatum: mechanisms of early drug reward

纹状体中的 FMRP:早期药物奖励机制

基本信息

项目摘要

Project Summary/Abstract Substance use disorders, affecting approximately 20.1 million individuals in the U.S., are characterized by a shift in voluntary drug-taking to compulsive drug-seeking and -taking behaviors, which persist despite negative consequences and remain prone to relapse after periods of abstinence. Though environmental influences have been identified as risk factors, there are major gaps in understanding of biological factors that contribute to the development of substance use disorders, limiting our ability to provide effective and lasting treatments. Previous work suggests that the fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates synaptic plasticity, is required for cocaine-induced synapse elimination in the striatum, a brain region critical to reward function. Moreover, loss of FMRP, either broadly or in the ventral striatum (nucleus accumbens; NAc), is capable of dampening cocaine-induced behaviors that are considered indicative of higher addiction-related risk. The main objective of this R36 application is to determine the mechanism by which FMRP facilitates operant self-administration of intravenous cocaine and reinstatement of drug-seeking behavior. The central hypothesis, based on published and preliminary data, is that FMRP positively mediates cocaine intravenous self-administration and reinstatement of drug-seeking via its regulation of the activity- regulated cytoskeleton-associated protein (Arc) in D1-receptor (D1R) expressing cells of the NAc. This hypothesis will be tested in two specific aims, each utilizing conditional knockdown approaches and an extensive self-administration assay that includes cue- and drug-induced reinstatement paradigms. Aim 1 will determine whether FMRP mediates these phenotypes via its function in specifically D1R or D2R cells of the NAc, while Aim 2 will determine whether FMRP’s regulation of Arc contributes to these phenotypes. This work will complete the applicant’s dissertation, as part of her training for a career in addiction-related science, provide insight into the mechanism by which FMRP mediates drug-related behaviors, providing critical direction for future studies aimed at identifying downstream targets for therapeutic intervention.
项目总结/摘要 物质使用障碍,影响美国约2010万人,的特征在于 自愿吸毒转变为强迫性吸毒和吸毒行为,尽管有负面影响, 结果,在禁欲期后仍然容易复发。虽然环境的影响 被确定为风险因素,但在理解导致死亡的生物因素方面存在重大差距。 物质使用障碍的发展,限制了我们提供有效和持久治疗的能力。 以前的研究表明,脆性X智力低下蛋白(FMRP),一种RNA结合蛋白, 调节突触可塑性,是可卡因诱导的纹状体(一个大脑区域)突触消除所必需的 对奖励功能至关重要。此外,FMRP的缺失,无论是广泛的还是在腹侧纹状体(核)中, NAc),能够抑制可卡因诱导的行为,这些行为被认为是高血压的标志。 成瘾相关风险本R36应用的主要目的是确定 FMRP促进静脉内可卡因的操作性自我给药和药物寻求的恢复 行为基于已发表的和初步的数据,中心假设是FMRP正介导 可卡因静脉自我给药和通过其活动的调节恢复药物寻求- 在NAc的D1受体(D1 R)表达细胞中调节的细胞凋亡相关蛋白(Arc)。这 假设将在两个特定的目标进行测试,每个目标都利用有条件的击倒方法, 广泛的自我给药试验,包括线索和药物诱导的恢复范例。目标1将 确定FMRP是否通过其在细胞的特异性D1 R或D2 R细胞中的功能介导这些表型。 NAc,而Aim 2将确定FMRP对Arc的调节是否有助于这些表型。这项工作 将完成申请人的论文,作为她在成瘾相关科学的职业生涯培训的一部分, 深入了解FMRP介导药物相关行为的机制,提供关键方向 用于未来的研究,旨在确定治疗干预的下游靶点。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Working around the CLOCK: Cocaine-induced phase shift of NPAS2 and SIRT1 and their roles in directing drug-related behaviour (commentary on Becker-Krail et al., 2021).
围绕时钟工作:可卡因诱导的 NPAS2 和 SIRT1 相移及其在指导药物相关行为中的作用(Becker-Krail 等人的评论,2021)。
Jugular Vein Catheter Design and Cocaine Self-Administration Using Mice: A Comprehensive Method.
{{ 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 }}

Jessica Huebschman其他文献

Jessica Huebschman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 }}

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 5.22万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了