Opioids and individual differences in social communication

阿片类药物与社交沟通中的个体差异

• 批准号: 8589605
• 负责人: Lauren V Riters
• 金额: $ 37.63万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-10 至 2017-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8589605
• 关键词: Affect; Affective; Anxiety; Apple; Area; Autistic Disorder; Back; Behavioral; Biological Models; Cations; Characteristics; Clinical; Communication; Communications Media; Copulation; Coupled; Courtship; Data; Disease; Dopamine; Food; Functional disorder; Goals; Heart; Human; Individual; Individual Differences; Intervention; Link; Measures; Mediating; Mental Depression; Mental disorders; Modeling; Motivation; Narcotic Antagonists; Neuropeptides; Opioid; Outcome; Play; Principal Investigator; Psychological reinforcement; Regulation; Research; Rewards; Role; Shapes; Site; Social Behavior; Social Environment; Social Interaction; Songbirds; Stimulus; Sturnus vulgaris; System; Testing; Time; United States National Institutes of Health; Western Blotting; Withdrawal; autism spectrum disorder; base; behavior influence; delta opioid receptor; design; emotional stimulus; innovation; insight; interest; male; medial preoptic nucleus; mu opioid receptors; neurochemistry; neuromechanism; novel; pleasure; preference; public health relevance; relating to nervous system; response; skills; social; social communication; social group; standard measure; ward

DESCRIPTION (provided by applicant): Social communication is at the heart of successful, healthy social interactions in humans. Social communication deficits are characteristic of several mental health disorders, including anxiety, depression, and autism spectrum disorders. Dysfunction in reward neural systems, including opioid neural systems, has been pro- posed to contribute to social communication deficits characteristic of these disorders, yet little research has focused on the role of reward neural systems in social communication. Furthermore, it is not clear why communication deficits associated with these disorders are observed in some but not other social contexts. One possibility supported by pilot data in a songbird model system is that communication in distinct social contexts is rewarded by distinct mechanisms. The long-term goal of the principal investigator is to identify the neurochemical mechanisms responsible for communication produced in distinct social contexts. The objective of this application is to identif the role of reward and opioid neuropeptides in the medial preoptic nucleus (mPOA) in communication in distinct social contexts. The mPOA regulates affiliative social behavior and communication, and opioid release in mPOA induces reward. In a songbird model, sexually-motivated communication (SMC) can result in immediate external reward (e.g., courtship song results in copulation). In contrast, general social communication (GSC) occurs in social groups in a non-sexual, affiliative context and does not result in immediate overt reward (e.g., copulation), suggesting GSC is linked to intrinsic reward. The central hypothesis sup- ported by strong preliminary data is that GSC is stimulated and maintained by an individual's intrinsic reward state induced by opioid release in mPOA. In contrast, SMC may be reinforced primarily by conspecific responses to song. Four specific aims based on strong pilot data in a songbird model system are proposed 1) to determine the extent to which opioid markers in mPOA relate to individual differences in GSC and SMC using Western immunoblots and quantitative real time PCR in starlings singing in distinct social contexts; 2) to determine the extent to which opioid markers in mPOA relate to intrinsic reward associated with GSC and SMC using conditioned place preference, a standard measure of reward; 3) to determine the extent to which opioids stimulate GSC and SMC using site-specific opioid pharmacological manipulations in mPOA; 4) to determine the extent to which opioid antagonists disrupt the link between reward and GSC by examining effects of opioid pharmacological manipulations in mPOA on song-associated reward measured using conditioned place preference. Results will elucidate links between opioids, reward, and communication produced within distinct social contexts. The research is innovative and significant because it will provide novel insight into neural mechanisms underlying the motivation to communicate and ways in which distinct reward mechanisms function to shape socially-appropriate behavioral interactions. Findings will reveal mechanisms that facilitate communication in select social contexts.

描述（由申请人提供）：社会沟通是人类成功，健康的社会互动的核心。社交障碍是几种精神疾病的特征，包括焦虑症、抑郁症和自闭症谱系障碍。奖励神经系统（包括阿片类神经系统）的功能障碍被认为是这些疾病的社会沟通缺陷的特征，但很少有研究关注奖励神经系统在社会沟通中的作用。此外，目前尚不清楚为什么在某些社会背景下会观察到与这些疾病相关的沟通缺陷，而在其他社会背景下却没有观察到。鸣鸟模型系统中的试验数据支持的一种可能性是，在不同的社会背景下，不同的机制奖励通信。首席研究员的长期目标是确定负责在不同的社会背景下产生的通信的神经化学机制。本应用的目的是确定奖励和阿片类神经肽在内侧视前核（mPOA）在不同的社会背景下的沟通中的作用。mPOA调节亲和性社会行为和交流，并且mPOA中的阿片样物质释放诱导奖励。在鸣鸟模型中，性动机交流（SMC）可以导致立即的外部奖励（例如，求偶歌导致交配）。相比之下，一般的社会交往（GSC）发生在非性的、亲和的环境中的社会群体中，并且不会导致直接的公开奖励（例如，交配），表明GSC与内在奖励有关。由强有力的初步数据支持的中心假设是，GSC由mPOA中阿片样物质释放诱导的个体内在奖赏状态刺激和维持。相反，SMC可能主要通过同种对歌曲的反应来加强。基于鸣禽模型系统中强有力的试点数据，提出了四个具体目标：1）使用Western免疫印迹和定量真实的时间PCR，确定mPOA中阿片样物质标记物与不同社会背景下鸣禽GSC和SMC个体差异的相关程度; 2）使用条件性位置偏爱确定mPOA中阿片样物质标记物与GSC和SMC相关的内在奖赏的相关程度，奖赏的标准测量; 3）使用mPOA中的位点特异性阿片样物质药理学操作来确定阿片样物质刺激GSC和SMC的程度; 4）通过检查mPOA中的阿片样物质药理学操作对使用条件性位置偏好测量的歌曲相关奖赏的影响来确定阿片样物质拮抗剂破坏奖赏和GSC之间的联系的程度。研究结果将阐明阿片类药物，奖励和不同的社会背景下产生的沟通之间的联系。这项研究具有创新性和重要性，因为它将为沟通动机的神经机制提供新的见解，以及不同的奖励机制在塑造社会适当的行为互动中的作用方式。研究结果将揭示在特定的社会环境中促进沟通的机制。