Investigating the role of GPR162 in hedonic behaviors

研究 GPR162 在享乐行为中的作用

• 批准号: 10215960
• 负责人: Laurie Sutton
• 金额: $ 14.59万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215960
• 关键词: Address; Anhedonia; Animal Model; Behavior; Behavioral; Bilateral; Binding; Brain; Cell Line; Communities; Data; Disease; Dissociation; Drug Targeting; Drug usage; Eating; Event; Food; G-Protein-Coupled Receptors; GTP Binding; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Gene Transfer; Genes; Goals; Guanosine Triphosphate; Heterotrimeric GTP-Binding Proteins; Home; In Vitro; Individual; Lentivirus Vector; Ligands; Liquid substance; Major Depressive Disorder; Measures; Mediating; Mental Depression; Metabolic; Modeling; Molecular; Mood Disorders; Motivation; Neurotransmitters; Nuclear; Nucleus Accumbens; Orphan; Palate; Pathologic; Pathway interactions; Personal Satisfaction; Pharmaceutical Preparations; Physiological; Plasmids; Process; Proteins; Psychological reinforcement; Reagent; Recombinants; Research; Resources; Rewards; Role; Sensory; Signal Pathway; Signal Transduction; Stress; Sucrose; System; Testing; Transcriptional Regulation; Venus; Vertebral column; Viral; behavior change; behavior influence; behavioral outcome; experience; experimental study; food consumption; gene cloning; hedonic; in vivo; knock-down; mouse model; neuropsychiatric disorder; neuropsychiatry; new therapeutic target; overexpression; pleasure; psychologic; receptor; response; rho GTP-Binding Proteins; small hairpin RNA; success; therapeutic target; tool

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.

抽象的 愉悦或有益的经历是一种自适应过程，对于健康的心理学至关重要 功能。体验愉悦的能力归因于个人的享乐主义语气或一个的“喜欢” 报酬。从病理上讲，低享乐主义语调或Anhedonia是体验愉悦的能力，这是一个关键特征 沮丧。可以通过对食物或液体的可口性来衡量享乐语调。最近，GPR162有 在享乐食品摄入量中暗示，这表明该接收器会导致与奖励相关的行为 设置享乐主义语调。 GPR162是孤儿G蛋白偶联受体（GPCR），因为其内源配体为 未知，是一个IDG合格的基因。该提案的目的是确定GPR162对享乐主义的作用 通过使用自然奖励（蔗糖）测量可口性来进一步检查其对其他人的贡献 奖励的各个方面，包括动机和加强。该项目将使用病毒介导的基因转移 在伏隔核中敲低或过表达GPR162的方法，该核是已知的介导的区域 与奖励相关的行为。最后，我们将开始解决GPR162的信号传导功能。我们的最初 体外发现显示GPR162激活RhoA途径。在这里，我们将将这一研究转移到我们的鼠标中 模型可以更好地了解GPR162信号传导。这项研究的结果将“阐明” 通过识别GPR162在奖励相关行为中的特定作用并通过产生 科学界的试剂和数据。