Investigating the role of GPR162 in hedonic behaviors

摘要 快乐或有益的经历是一种适应过程，对健康的心理是必不可少的 功能正常。体验快乐的能力归因于一个人的享乐主义基调或对 奖励。病理上，低享乐基调或快感缺乏症是体验快乐的能力，这是 抑郁症。享乐基调可以通过对食物或液体的适口性来衡量。最近，GPR162已经 与享乐性食物摄取有关，这表明该受体通过 设置享乐基调。GPR162是一种孤儿G蛋白偶联受体，其内源性配体是 未知，是IDG合格基因。这项提案的目标是确定GPR162在享乐方面的作用 通过使用自然奖励(蔗糖)来测量适口性，并进一步考察其对其他 奖励的各个方面，包括激励和强化。这个项目将使用病毒介导的基因转移 伏隔核中GPR162基因表达下调或过表达的途径 与奖励相关的行为。最后，我们将开始讨论GPR162的信令功能。我们最初的进站 体外研究结果表明，GPR162激活了RhoA途径。在这里，我们将把这项研究转移到我们的鼠标上 模型，以更好地了解GPR162信令。这项研究的结果将“照亮” 通过确定GPR162在奖赏相关行为中的特定作用以及通过生成 为科学界提供试剂和数据。

Abstract Pleasure or rewarding experiences serves as an adaptive process and are essential for healthy psychological functioning. The ability to experience pleasure is attributed to an individual’s hedonic tone or the ‘liking’ of a reward. Pathologically, low hedonic tone or anhedonia is the ability to experience pleasure, a key feature in depression. Hedonic tone can be measured by the palatability towards food or liquids. Recently, GPR162 has been implicated in hedonic food intake suggesting that this receptor contributes to reward-related behaviors by setting hedonic tone. GPR162 is an orphan G protein coupled receptor (GPCR) as its endogenous ligand is unknown and is an IDG eligible gene. The goal of this proposal is to identify the role of GPR162 towards hedonic tone by measuring palatability using a natural reward (sucrose) and to further examine its contribution to other aspects of reward including motivation and reinforcement. This project will use a viral mediated gene transfer approach to either knockdown or overexpress GPR162 in the nucleus accumbens, a region known to mediate reward-related behaviors. Finally, we will begin to address the signaling capabilities of GPR162. Our initial in vitro findings show GPR162 activates the RhoA pathway. Here we will move this line of research into our mouse models to gain a better understanding of GPR162 signaling. The results of this study will “illuminate” an understudied protein by identifying the specific role of GPR162 in reward-related behaviors and by generating reagents and data for the scientific community.