Dopaminergic regulation of aversion-motivated behaviors

厌恶动机行为的多巴胺能调节

基本信息

  • 批准号:
    10680079
  • 负责人:
  • 金额:
    $ 3.26万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-28 至 2026-08-27
  • 项目状态:
    未结题

项目摘要

Project Summary Negative experiences influence everyone's daily lives by altering emotional states, decision making, and motivated behavior. For those with substance abuse disorders attempting to remain abstinent, such experiences are clinically relevant as they are often described as a primary trigger to relapse. Similarly, negative experiences can trigger or exacerbate mood disorders such as depression. In order to develop ways to protect against the detrimental impact of these negative experiences, it is critical to understand the neural mechanisms by which aversive stimuli affect motivation. Decades of research has shown the nucleus accumbens (NAc) to be a key region for affective processes to impact behavior. Thus, it is important to understand how negative experiences affect mesolimbic dopamine signaling and the impact that has on motivated behaviors. Research from our lab suggests that aversive stimuli promote drug-taking and also decrease nucleus accumbens dopamine. The central hypothesis in this proposal is that negative experiences reduce mesoaccumbens dopamine and that it is this reduction which causes the increased motivated behavior we have seen following exposure to aversive stimuli. Aim 1 will test the necessity and sufficiency of aversion-induced dopamine changes to alter escape behavior. Preliminary data from our lab show that rats will perform an operant response to terminate an aversive white noise. I will use optogenetics to manipulate dopamine release to both mimic and counteract the typical white noise-induced reduction in dopamine. Aim 2 will test the necessity and sufficiency of aversion-induced dopamine reductions to alter drug-taking behavior. Our preliminary data show that white noise both reduces dopamine and increases drug-taking. This experiment will leverage chemogenetics and photometry to both manipulate and measure dopamine release during drug self-administration. Aim 3 will test the impact of prior chronic variable stress on the sensitivity to aversive stimuli. I will use photometry to characterize naturally occurring dopamine levels following chronic stress, then test if chronic stress also changes the sensitivity to aversive stimuli in a punishment paradigm. I am confident that the training and mentorship of Drs. Robert Wheeler, Marieke Gilmartin, and John Mantsch throughout the research and training aspects of this fellowship will expand on my experimental skills to successfully complete the proposed research, as well as gain professional skills that will equip me for a postdoctoral position. This fellowship will thus help me achieve my ultimate goal to develop an independent research program at an academic institution that also permits me to engage in regular teaching responsibilities.
项目摘要 消极的经历通过改变情绪状态、决策和行为来影响每个人的日常生活。 动机行为对于那些试图保持禁欲的药物滥用障碍患者来说, 具有临床相关性,因为它们通常被描述为复发的主要触发因素。同样,负面的经历 会引发或加重抑郁症等情绪障碍。为了制定办法, 这些负面经验的有害影响,关键是要了解神经机制, 厌恶性刺激影响动机。几十年的研究表明,核神经元(NAc)是一个关键, 情感过程影响行为的区域。因此,重要的是要了解负面经历如何 影响中脑边缘多巴胺信号传导以及对动机行为的影响。我们实验室的研究 表明,厌恶性刺激促进吸毒,也减少了脑桥核多巴胺。的 这个建议的中心假设是,负面的经历会减少中脑多巴胺, 这种减少导致我们在接触厌恶性物质后看到的动机行为增加, 刺激。 目的1将测试厌恶诱导的多巴胺变化改变逃避行为的必要性和充分性。 我们实验室的初步数据表明,大鼠会执行一个操作性反应,以终止一个厌恶的白色 噪声我将使用光遗传学来操纵多巴胺的释放,以模拟和抵消典型的白色 噪音引起的多巴胺减少目的2将检验厌恶诱发多巴胺的必要性和充分性 减少以改变吸毒行为。我们的初步数据表明,白色噪音既减少多巴胺, 增加吸毒。该实验将利用化学遗传学和光度学来操纵和测量细胞。 测量药物自我给药期间多巴胺的释放。目标3将检验既往慢性变量的影响 强调对厌恶刺激的敏感性。我会用光度法来描述自然产生的多巴胺 水平,然后测试慢性压力是否也会改变对厌恶刺激的敏感性。 惩罚范式 我相信,罗伯特惠勒博士、玛丽克·吉尔马丁博士和约翰·曼奇博士的培训和指导 在整个研究和培训方面的奖学金将扩大我的实验技能, 成功完成拟议的研究,以及获得专业技能,将装备我一个 博士后职位这个奖学金将帮助我实现我的最终目标,发展一个独立的 我在学术机构的一个研究项目,也允许我从事正常的教学责任。

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 }}

Elaine Grafelman其他文献

Elaine Grafelman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

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 3.26万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了