Sex-dependent regulation of social reward by oxytocin in the mesolimbic reward circuitry

中脑边缘奖励回路中催产素对社会奖励的性别依赖性调节

• 批准号: 10569581
• 负责人: H. Elliott Albers
• 金额: $ 52.16万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-06 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569581
• 关键词: Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Data; Development; Disease; Dopamine; Dose; Female; Gender; Goals; Hamsters; Hypothalamic structure; Incidence; Knowledge; Lateral; Maintenance; Measures; Medial; Mediating; Mesocricetus auratus; Neurodevelopmental Disorder; Neurons; Nucleus Accumbens; Oxytocin; Oxytocin Receptor; Periodicity; Prefrontal Cortex; Prevalence; Property; Publishing; Receptor Activation; Regulation; Rewards; Rodent; Role; Same-sex; Scanning; Series; Sex Differences; Shapes; Site; Social Behavior; Social Interaction; Social Values; Stimulus; Symptoms; System; Testing; Ventral Tegmental Area; dopamine system; drug of abuse; improved; male; mesolimbic system; neural circuit; neurochemistry; neuromechanism; neuropsychiatric disorder; novel; preference; pressure; response; reward circuitry; sex; small hairpin RNA; social; social relationships; translational potential

PROJECT SUMMARY The rewarding properties of social interactions are critical to the expression of adaptive social behavior and to the development and maintenance of social relationships. Little is known, however, about the factors that determine the reward value of social interactions or about the basic neural mechanisms that underlie social reward, particularly in females. We do know that the mesolimbic dopamine system (MDS) is central to the neural circuitry controlling the rewarding properties of many other stimuli such as drugs of abuse. A primary component of the MDS is dopamine (DA)-containing neurons in the ventral tegmental area (VTA) that project to the nucleus accumbens (NAc) as well as to other sites such as the medial prefrontal cortex. Critical inputs to the MDS include oxytocin (OT)-containing projections from the hypothalamus. We and others have demonstrated that, in male rodents, activation of OT receptors in the caudal VTA and in the NAc is essential for the rewarding properties of social interaction. Remarkably, despite the considerable evidence for sex differences in OT regulation of social behaviors, the role of OT in regulating social reward in females has not been investigated. This project will provide substantial new information on the factors that determine the reward value of social interactions and on the neural mechanisms that mediate social reward by testing this series of integrated hypotheses in male and female Syrian hamsters. Based on published and preliminary data from our lab and others, we have hypothesized that: 1) there is an inverted U relationship between the “dose” of social interactions and social reward, 2) this dose-response relationship is initiated at lower doses in females than in males, and 3) this sex difference is mediated by differential OT-induced DA release in the MDS. This project has substantial potential for translation to clinically-related problems by providing: 1) new information on how social stimuli can transition from being rewarding to being less rewarding or even aversive, 2) potential mechanisms for understanding well-known sex differences in the incidence of neuropsychiatric and neurodevelopmental disorders for which dysfunctional social relationships are an important symptom, and 3) the potential for development of gender- specific treatments for these disorders.

项目摘要 社会互动的回报特性对于适应性社会行为的表达和 社会关系的发展和维护。然而，人们对这些因素知之甚少， 确定社交互动的奖励价值或社交互动的基本神经机制 奖励，尤其是女性。我们知道，中脑边缘多巴胺系统（MDS）是中枢神经系统， 控制许多其他刺激（如滥用药物）的奖赏特性的神经回路。主 MDS的组成部分是腹侧被盖区（VTA）的多巴胺（DA）神经元， 到脑桥核（NAc）以及到其他部位如内侧前额叶皮质。关键投入 包括来自下丘脑的含有催产素（OT）的投射。我们和其他人已经 证明，在雄性啮齿动物中，尾侧腹侧被盖区和腹侧被盖区中OT受体的激活是 对社会互动的回报特性至关重要。值得注意的是，尽管 OT调节社会行为的性别差异的证据，OT在调节社会奖励中的作用， 女性没有被调查。该项目将提供大量新的信息，说明 确定社会互动的奖励价值和调节社会奖励的神经机制 通过在雄性和雌性叙利亚仓鼠中测试这一系列综合假设。基于已发表 根据我们实验室和其他人的初步数据，我们假设：1）存在一个倒U形 社会互动的"剂量"和社会奖励之间的关系，2）这种剂量反应 雌性动物在较低剂量下开始产生关系，3）这种性别差异是介导的 通过在MDS中差异OT诱导的DA释放。该项目具有巨大的翻译潜力， 临床相关的问题，通过提供：1）新的信息，社会刺激如何可以过渡到被 从奖励到不那么奖励甚至厌恶，2）理解众所周知的潜在机制 神经精神和神经发育障碍发病率的性别差异， 功能失调的社会关系是一个重要的症状，和3）性别发展的潜力- 针对这些疾病的特殊治疗。