Opioids and individual differences in social communication

描述(申请人提供)：社会交流是人类成功、健康的社会交往的核心。社交障碍是几种精神健康障碍的特征，包括焦虑、抑郁和自闭症谱系障碍。包括阿片类神经系统在内的奖赏神经系统的功能障碍被认为是导致这些障碍所特有的社会沟通障碍的原因之一，但很少有研究关注奖赏神经系统在社会沟通中的作用。此外，目前还不清楚为什么与这些障碍相关的沟通障碍会在一些社会环境中观察到，而不是在其他社会环境中观察到。在鸣禽模型系统中，试点数据支持的一种可能性是，在不同的社会背景下的交流得到了不同的机制的奖励。首席研究人员的长期目标是确定在不同的社会背景下产生的沟通的神经化学机制。该应用的目的是确定内侧视前核(MPOA)中的奖赏和阿片神经肽在不同社会背景下的交流中的作用。MPOA调节附属的社会行为和交流，而mPOA中阿片类药物的释放产生奖励。在鸣禽模型中，性动机交流(SMC)可以产生直接的外部奖励(例如，求爱歌曲导致交配)。相比之下，一般社会交流(GSC)发生在非性的、附属的社会群体中，不会导致直接的公开奖励(例如交配)，这表明GSC与内在奖励有关。强大的初步数据支持的中心假说是，GSC是由mPOA中阿片类药物释放诱导的个体内在奖赏状态刺激和维持的。相反，SMC可能主要通过对歌曲的同种特异性反应而得到加强。在鸣禽模型系统中，基于强大的飞行员数据，提出了四个具体目标：1)使用免疫印迹和实时定量聚合酶链式反应来确定mPOA中阿片标记与GSC和SMC的个体差异的程度；2)使用条件位置偏爱来确定mPOA中阿片标记与GSC和SMC相关的内在奖赏的程度；3)使用mPOA中阿片类药物的部位特异性药理操作来确定阿片类药物刺激GSC和SMC的程度；4)通过检测mPOA阿片类药物操作对条件位置偏爱测量的歌曲相关奖赏的影响，确定阿片拮抗剂在多大程度上干扰奖赏和GSC之间的联系。结果将阐明在不同的社会背景下产生的阿片类药物、奖励和交流之间的联系。这项研究具有创新性和重要意义，因为它将为沟通动机背后的神经机制提供新的见解，以及不同的奖励机制如何发挥作用来塑造社交适当的行为互动。研究结果将揭示在特定的社会背景下促进沟通的机制。

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.