Neuroimaging Correlates of Cocaine Reinforcement for Cognitive Performance

可卡因强化认知表现的神经影像学相关性

基本信息

项目摘要

DESCRIPTION (provided by applicant): The purpose of this research project is to assess changes in the brains of nonhuman primates (NHPs) during information processing in a cognitive task that involves exposure to cocaine as a reward for successful performance. Evidence is presented that structures in the brain of NHPs are affected by the introduction of cocaine as a reward on signaled trials within a session where appetitive (juice) rewards are also available. The Project will utilize a well-characterized short-term memory/executive function paradigm consisting of a multi- object delayed match to sample (DMS) task. The task provides for testing whether the "cognitive load" on any given trial is directly related to performance in association with the functional neuronal activity in prefrontal cortex (PFC), medial temporal lobe (MTL) and dorsal and ventral striatum (Str) that is imaged from the same behavioral sessions. The proposed studies will determine how cognitive processing is affected by acute and long-term exposure to cocaine in this paradigm and how agents currently utilized in human clinical studies alter the detrimental effects of cocaine on cognitive function. Aims 1 and 2 will assess and characterize PET imaging of 18FDG brain metabolic activity in the above three brain regions and determine the effects of cocaine rewards on performance of the DMS task. Aim 3 will examine the effects of cocaine rewarded cognitive performance as a function of the animal's preference for choosing cocaine vs. juice signaled trials. These analyses will partial out cocaine effects across individual animals in terms of their choice of cocaine vs. juice trials and examine difference in PET imaging of 18FDG brain metabolic activity in the above three brain regions to determine functional differences in animals that prefer cocaine vs. juice rewarded trials in the same DMS paradigm. Aim 3 will also extend the above analyses to animals that are repeatedly exposed to conditions in which cocaine and appetitive rewards are implemented in the same random manner during day-to-day testing for a period of six months. Changes in DMS responding (performance) and preferences for cocaine vs. juice rewards and associated neuronal correlates over this time period will be determined as a baseline for in order to ascertaining the long-term effectiveness of agents administered as part of Aim 4. Aim 4 will examine how the above behavioral and 18FDG imaging correlates of cognitive demand in the DMS task change as a function of prior treatment with two candidate treatment agents, Modafinil and the hypocretin-1 receptor antagonist SB334867, that can alter cocaine's reinforcing effects in self-administration paradigms and are currently considered as possible compounds to treat cocaine addiction in human clinical trials. These actions of these drugs in the early phase of testing will be compared with the effects following long-term exposure to the same paradigm using performance and preference measures as indicants of changes in cocaine's actions in association with altered 18FDG imaging correlates. PUBLIC HEALTH RELEVANCE: The relevance of this Project to public health is directly related to finding agents and drugs that will alleviate the dependence on substances that are abused in society. Primarily the Program will focus on the effects of cocaine on cognition in nonhuman primates which serves as the final testbed for candidate drugs that can lead to therapeutic treatment of cocaine abusers.
描述(由申请人提供):本研究项目的目的是评估非人类灵长类动物(NHPs)在认知任务中信息处理过程中的大脑变化,该任务涉及暴露于可卡因作为成功表现的奖励。有证据表明,在有食欲(果汁)奖励的情况下,在信号试验中引入可卡因作为奖励会影响NHPs的大脑结构。该项目将利用具有良好特征的短期记忆/执行功能范例,包括多对象延迟匹配样本(DMS)任务。该任务提供测试任何给定试验中的“认知负荷”是否与在相同行为会话中成像的前额叶皮层(PFC)、内侧颞叶(MTL)和背腹纹状体(Str)的功能性神经元活动的表现直接相关。拟议的研究将确定在这种模式下,急性和长期暴露于可卡因如何影响认知加工,以及目前在人类临床研究中使用的药物如何改变可卡因对认知功能的有害影响。目的1和2将评估和表征上述三个脑区18FDG脑代谢活动的PET成像,并确定可卡因奖励对DMS任务表现的影响。目的3将检验可卡因奖励的认知表现的影响,作为动物对选择可卡因和果汁信号试验的偏好的功能。这些分析将在个体动物选择可卡因和果汁试验方面部分排除可卡因的影响,并检查上述三个脑区18FDG脑代谢活动的PET成像差异,以确定在相同的DMS模式下,更喜欢可卡因和果汁奖励试验的动物的功能差异。目标3还将上述分析扩展到在六个月的日常测试中反复暴露于可卡因和食欲奖励以同样随机方式实施的条件下的动物。在这段时间内,DMS对可卡因和果汁奖励的反应(表现)和偏好以及相关神经元相关性的变化将被确定为基线,以确定作为Aim 4的一部分施用的药物的长期有效性。目的4将研究DMS任务中认知需求的上述行为和18FDG成像相关因素如何随着两种候选治疗药物(莫达非尼和下丘脑分泌素-1受体拮拮剂SB334867)的预先治疗而变化,这两种候选治疗药物可以改变可卡因在自我给药范式中的强化作用,目前被认为是人类临床试验中治疗可卡因成瘾的可能化合物。这些药物在试验早期阶段的作用将与长期暴露于同一范式后的效果进行比较,使用性能和偏好测量作为可卡因作用变化与18FDG成像相关改变的指标。

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 }}

SAMUEL A. DEADWYLER其他文献

SAMUEL A. DEADWYLER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('SAMUEL A. DEADWYLER', 18)}}的其他基金

Modulation of Radiation-induced Brain Injury in the Nonhuman Primate
非人类灵长类动物辐射引起的脑损伤的调节
  • 批准号:
    8824880
  • 财政年份:
    2012
  • 资助金额:
    $ 31.88万
  • 项目类别:
Modulation of Radiation-induced Brain Injury in the Nonhuman Primate
非人类灵长类动物辐射引起的脑损伤的调节
  • 批准号:
    8293574
  • 财政年份:
    2012
  • 资助金额:
    $ 31.88万
  • 项目类别:
Modulation of Radiation-induced Brain Injury in the Nonhuman Primate
非人类灵长类动物辐射引起的脑损伤的调节
  • 批准号:
    8461136
  • 财政年份:
    2012
  • 资助金额:
    $ 31.88万
  • 项目类别:
Neuroimaging Correlates of Cocaine Reinforcement for Cognitive Performance
可卡因强化认知表现的神经影像学相关性
  • 批准号:
    8580552
  • 财政年份:
    2009
  • 资助金额:
    $ 31.88万
  • 项目类别:
Neuroimaging Correlates of Cocaine Reinforcement for Cognitive Performance
可卡因强化认知表现的神经影像学相关性
  • 批准号:
    8411990
  • 财政年份:
    2009
  • 资助金额:
    $ 31.88万
  • 项目类别:
Neuroimaging Correlates of Cocaine Reinforcement for Cognitive Performance
可卡因强化认知表现的神经影像学相关性
  • 批准号:
    8214610
  • 财政年份:
    2009
  • 资助金额:
    $ 31.88万
  • 项目类别:
Neuronal Analysis of Cocaine Effects on Cognition
可卡因对认知影响的神经元分析
  • 批准号:
    7489960
  • 财政年份:
    2007
  • 资助金额:
    $ 31.88万
  • 项目类别:
Neuronal Analysis of Cocaine Effects on Cognition
可卡因对认知影响的神经元分析
  • 批准号:
    7880787
  • 财政年份:
    2007
  • 资助金额:
    $ 31.88万
  • 项目类别:
Neuronal Analysis of Cocaine Effects on Cognition
可卡因对认知影响的神经元分析
  • 批准号:
    8117259
  • 财政年份:
    2007
  • 资助金额:
    $ 31.88万
  • 项目类别:
Neuronal Analysis of Cocaine Effects on Cognition
可卡因对认知影响的神经元分析
  • 批准号:
    7299966
  • 财政年份:
    2007
  • 资助金额:
    $ 31.88万
  • 项目类别:

相似海外基金

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:
    $ 31.88万
  • 项目类别:
    Standard 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:
    $ 31.88万
  • 项目类别:
    Standard Grant
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:
    $ 31.88万
  • 项目类别:
    Training 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:
    $ 31.88万
  • 项目类别:
    Fellowship
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:
    $ 31.88万
  • 项目类别:
    Research Grant
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:
    $ 31.88万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
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:
    $ 31.88万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 31.88万
  • 项目类别:
    Standard Grant
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:
    $ 31.88万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 31.88万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了