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 社会互动的奖励性能对于自适应社会行为的表达至关重要 社会关系的发展和维护。 确定社会互动的奖励价值或基于社会基础的基本神经机制 奖励，特别是在女性中。 控制许多其他刺激的奖励性能，例如滥用药物 MDS的成分是多巴胺（DA） - 腹侧对段区域（VTA）的神经元 伏隔核（NAC）以及其他部位，例如内​​侧前额叶皮层 对MDS包括催产素（OT） - 含有假设的投影。 证明在雄性啮齿动物中，在尾vta和NAC中激活OT受体 对于社会互动的奖励特性至关重要。 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 尚未对女性进行调查。 确定社会互动的奖励价值和内侧社会奖励的神经机制 通过基于公开的男性和女性叙利亚仓鼠的一系列综合假设 以及我们实验室和其他人的初步数据，我们假设：1）有一个倒立的u 社会互动与社会奖励的“剂量”之间的关系，2）这种剂量痛苦 与男性相比，女性的关系以低剂量开始，3）这种性别差异是介导的 通过差异OT诱导的DA释放在MDS中。 通过提供与临床有关的问题：1）有关社会刺激如何过渡的新信息 奖励减少有益甚至厌恶性的奖励，2）理解知名的潜在机制 神经精神病学和神经发育障碍的发生率的性别差异 功能失调的社会关系是重要的症状，3）发展性别的潜力 疾病的特定治疗方法。