Behavioral and Neural Bases of Combining Oxytocin and Naloxone for Optimally Enhancing Interactive Social Attention

结合催产素和纳洛酮优化增强互动社交注意力的行为和神经基础

基本信息

  • 批准号:
    10630140
  • 负责人:
  • 金额:
    $ 52.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-14 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary Several clinical trials have found that intranasal oxytocin (OT) treatment is not practically viable in its current form for improving core social symptoms in autism spectrum disorders (ASD). The current intranasal OT treatment has been criticized for its often weak and inconsistent effects, demanding an important need to explore new ways to improve its efficacy and reliability in modulating the OT system. While much less studied, the central opioid system has also been implicated in ASD based on the opioid dysregulation found in certain cases of ASD, as well as the well-known modulatory effects of opioid agonists, such as morphine, and its receptor antagonists, such as naloxone (NAL), in regulating social behaviors. In this translational non-human primate proposal, we will investigate a new alternative therapeutic option in improving core social functions by exploiting the robust regulatory relationship between the central OT and opioid systems. Our pharmacological study in non-human primates recently provided a proof of concept of this combined pharmacological approach in more effectively modulating social attention. The combined intranasal administration of OT and NAL (OTNAL) enhanced spontaneous social attention and contingent gaze dynamics following interactive eye contact over and beyond the summed effects from administering OT alone and NAL alone, indicating a combinatorial benefit of OTNAL. Capitalizing on this finding, we now propose to determine the optimal doses of OT and NAL in the combined OTNAL format, its corresponding cerebrospinal fluid markers of successful OTNAL interventions, as well as the neurophysiological markers underlying the combinatorial benefits in the domain of social attention. We will first obtain comprehensive dose-response functions for the OTNAL intervention during spontaneously occurring real- life social gaze interactions and assess the corresponding changes in cerebrospinal fluid OT levels due to OTNAL compared to other conditions (Aim 1A, 1B). We will then study how neural activity patterns within and across two key brain nodes in social processing, the amygdala and the anterior cingulate cortex, are impacted by OTNAL (Aim 2). Finally, we will test causal contributions of these two regions for the OTNAL effects by blocking OT-binding receptor types focally in these areas (Aim 3). The results from this work will offer novel mechanistic insights into the combined pharmacological approach using OTNAL to more vigorously promote social engagements in the primate brain. Such results will help set the stage for translating the combinatorial benefit of using intranasal OTNAL for more effectively and reliably reducing core social symptoms in ASD.
项目摘要 几项临床试验已经发现,鼻内催产素(OT)治疗在其目前的治疗中实际上是不可行的。 用于改善自闭症谱系障碍(ASD)的核心社会症状。当前的鼻内OT 治疗一直被批评其往往薄弱和不一致的效果,要求一个重要的需要探索 新的方法,以提高其效率和可靠性,在调制OT系统。虽然研究得较少,但中央 阿片样物质系统也与ASD有关,这是基于在某些ASD病例中发现的阿片样物质失调, 以及阿片样物质激动剂如吗啡及其受体拮抗剂的众所周知的调节作用, 如纳洛酮(NAL),在调节社会行为。在这个翻译的非人类灵长类动物的建议,我们将 研究一种新的替代治疗选择,通过利用强大的 中枢OT和阿片系统之间的调节关系。我们在非人类的药理学研究 灵长类动物最近提供了这种联合药理学方法的概念证明, 调节社会注意力。OT和NAL联合鼻内给药(OTNAL)可增强 在交互式目光接触之后自发社会注意和偶然注视动态 单独给予OT和单独给予NAL的总效应表明OTNAL的组合益处。 利用这一发现,我们现在建议确定OT和NAL在组合中的最佳剂量。 OTNAL格式,其相应的成功OTNAL干预的脑脊液标志物,以及 神经生理学标志物在社会注意力领域的组合效益。我们将首先 在自发发生的真实的- 生活社会凝视互动,并评估脑脊液OT水平的相应变化, OTNAL与其他条件相比(目标1A,1B)。然后,我们将研究神经活动模式, 大脑中两个重要的社交处理节点杏仁核和前扣带皮层受到影响 (二)目标(Aim)最后,我们将测试这两个区域对OTNAL效应的因果贡献, 阻断这些区域中的OT结合受体类型(Aim 3)。这项工作的结果将提供新颖的 使用OTNAL的联合药理学方法的机制见解,以更有力地促进 灵长类大脑中的社交活动这些结果将有助于为翻译组合 使用鼻内OTNAL更有效、更可靠地减少ASD核心社交症状的益处。

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)
Oxytocin does not stand alone.
{{ 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 }}

Steve Wohn Chul Chang其他文献

Steve Wohn Chul Chang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('Steve Wohn Chul Chang', 18)}}的其他基金

Neural investigations into cooperative social interactions in marmoset dyads
狨猴二人组合作社会互动的神经研究
  • 批准号:
    10369856
  • 财政年份:
    2022
  • 资助金额:
    $ 52.68万
  • 项目类别:
Neural investigations into cooperative social interactions in marmoset dyads
狨猴二人组合作社会互动的神经研究
  • 批准号:
    10551217
  • 财政年份:
    2022
  • 资助金额:
    $ 52.68万
  • 项目类别:
Prefrontal and Amygdalar Mechanisms of Live Social Gaze Interaction
实时社交凝视互动的前额叶和杏仁核机制
  • 批准号:
    10670053
  • 财政年份:
    2022
  • 资助金额:
    $ 52.68万
  • 项目类别:
Behavioral and Neural Bases of Combining Oxytocin and Naloxone for Optimally Enhancing Interactive Social Attention
结合催产素和纳洛酮优化增强互动社交注意力的行为和神经基础
  • 批准号:
    10406985
  • 财政年份:
    2019
  • 资助金额:
    $ 52.68万
  • 项目类别:
Behavioral and Neural Bases of Combining Oxytocin and Naloxone for Optimally Enhancing Interactive Social Attention
结合催产素和纳洛酮优化增强互动社交注意力的行为和神经基础
  • 批准号:
    10176600
  • 财政年份:
    2019
  • 资助金额:
    $ 52.68万
  • 项目类别:
Behavioral and Neural Bases of Combining Oxytocin and Naloxone for Optimally Enhancing Interactive Social Attention
结合催产素和纳洛酮优化增强互动社交注意力的行为和神经基础
  • 批准号:
    9796897
  • 财政年份:
    2019
  • 资助金额:
    $ 52.68万
  • 项目类别:
Toward A Macaque Model Of Social Brain Dysfunction In Real-Life Social Interactions
现实生活中社交互动中社交脑功能障碍的猕猴模型
  • 批准号:
    9900591
  • 财政年份:
    2016
  • 资助金额:
    $ 52.68万
  • 项目类别:
Toward A Macaque Model Of Social Brain Dysfunction In Real-Life Social Interactions
现实生活中社交互动中社交脑功能障碍的猕猴模型
  • 批准号:
    9309071
  • 财政年份:
    2016
  • 资助金额:
    $ 52.68万
  • 项目类别:
Role of Oxytocin in the Amygdala-Prefrontal Network During Social Decision-Making
催产素在社会决策过程中杏仁核前额叶网络中的作用
  • 批准号:
    8878644
  • 财政年份:
    2014
  • 资助金额:
    $ 52.68万
  • 项目类别:
Role of Oxytocin in the Amygdala-Prefrontal Network During Social Decision-Making
催产素在社会决策过程中杏仁核前额叶网络中的作用
  • 批准号:
    8894608
  • 财政年份:
    2014
  • 资助金额:
    $ 52.68万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了