Opioids and individual differences in social communication

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。社会沟通缺陷是一些精神健康障碍的特征，包括焦虑、抑郁和自闭症谱系障碍。奖赏神经系统（包括阿片神经系统）的功能障碍被认为是导致这些障碍的社会交际缺陷的原因之一，但很少有研究关注奖赏神经系统在社会交际中的作用。此外，尚不清楚为什么与这些障碍相关的沟通缺陷在某些社会环境中被观察到，而在其他社会环境中却没有。鸣禽模型系统的试验数据支持的一种可能性是，在不同的社会背景下的交流受到不同机制的奖励。首席研究员的长期目标是确定在不同的社会环境中负责交流的神经化学机制。本应用程序的目的是确定奖励和阿片神经肽在内侧视前核（mPOA）在不同社会背景下的交流中的作用。mPOA调节亲和性社会行为和交流，而mPOA中的阿片释放诱导奖励。在鸣禽模型中，性动机交流（SMC）可以导致直接的外部奖励（例如，求偶歌曲导致交配）。相比之下，一般社会交流（GSC）发生在社会群体中，是在非性的、附属的环境中，不会导致立即的公开奖励（例如交配），这表明GSC与内在奖励有关。强有力的初步数据支持的中心假设是，GSC是由mPOA中阿片释放引起的个体内在奖励状态刺激和维持的。相反，SMC可能主要通过对歌曲的同特异性反应得到加强。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)利用Western免疫印迹和定量实时PCR确定mPOA中阿片标记与不同社会背景下鸣叫的椋鸟GSC和SMC个体差异的关系程度；2)确定mPOA中的阿片标记物与GSC和SMC相关的内在奖励的关联程度，使用条件位置偏好（一种标准的奖励措施）；3)确定阿片类药物在mPOA中使用特定部位的阿片类药物操作刺激GSC和SMC的程度；4)通过检查mPOA中阿片药物操作对使用条件位置偏好测量的歌曲相关奖励的影响，确定阿片拮抗剂在多大程度上破坏了奖励与GSC之间的联系。结果将阐明阿片类药物、奖励和在不同社会背景下产生的交流之间的联系。这项研究具有创新性和重要意义，因为它将为交流动机背后的神经机制以及不同的奖励机制如何塑造社会适当的行为互动提供新的见解。研究结果将揭示在特定的社会环境中促进交流的机制。

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.