Sex Differences in the Social Brain

社交大脑中的性别差异

• 批准号: 9310365
• 负责人: H. Elliott Albers
• 金额: $ 67.53万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-05 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9310365
• 关键词: Aggressive behavior; Agonist; Agonistic Behavior; Anxiety Disorders; Attention; Behavioral; Binding; Brain; Clinical; Confocal Microscopy; Data; Development; Drug Targeting; Exhibits; Female; Fluoxetine; Gender; Goals; Hamsters; Health; Hypothalamic structure; Incidence; Individual; Injection of therapeutic agent; Knowledge; Lead; Macaca mulatta; Maintenance; Mesocricetus auratus; Mood Disorders; Neurons; Outcome; Pattern; Pharmacotherapy; Phenotype; Physiological; Positron-Emission Tomography; Predisposition; Receptor Activation; Receptor Inhibition; Resistance; Role; Selective Serotonin Reuptake Inhibitor; Series; Serotonin; Serotonin Receptor 5-HT1A; Sex Characteristics; Site; Social Interaction; Social status; Stress; Testing; Therapeutic; Vasopressins; Woman; Work; coping; drug development; innovation; male; men; neurochemistry; neuromechanism; neuropsychiatric disorder; receptor; receptor binding; social; social stress; stem

PROJECT SUMMARY In most mammalian species, social interactions among individuals of the same species are governed by dominance relationships. These hierarchical relationships are established and maintained by agonistic behaviors, including aggression. Importantly, recent data indicate that the neural mechanisms underlying aggression and attaining dominance produce a phenotype that is resistant to social stress while the mechanisms underlying subordinate status produce a social stress-susceptible phenotype that may result in a number of adverse behavioral and physiological outcomes. Despite the relationship between social status and stress, the neurochemical mechanisms that underlie dominance have received only limited attention in males and almost no attention in females. This project will fill this critical gap in our knowledge by testing an integrated series of hypotheses using Syrian hamsters and rhesus monkeys. This project will critically test the overarching hypothesis that the agonistic behaviors responsible for the formation and maintenance of dominance relationships are regulated in dramatically different ways by vasopressin (AVP) and serotonin (5- HT) in males and females. Specifically, we propose that activation of AVP and inhibition of 5-HT promotes dominant status and a stress resistant phenotype in MALES while producing subordinate status and a stress susceptible phenotype in FEMALES. In contrast, inhibition of AVP and activation of 5-HT promotes dominance and a stress resistant phenotype in FEMALES while producing subordinate status and a stress susceptible phenotype in MALES. Together, these data will significantly expand our knowledge of sex differences in the neurochemical mechanisms that define social phenotypes and will provide innovative gender specific strategies for promoting resistance to social stress. The data obtained in this project could have an almost immediate clinical impact by guiding drug treatments for stress reduction in men and women as well as guiding drug development by emphasizing the role of AVP-targeted drugs in males and 5-HT- targeted drugs in females.

项目摘要 在大多数哺乳动物物种中，同一物种的个体之间的社会互动由以下因素支配： 支配关系这些等级关系是由竞争性的 行为，包括侵略。重要的是，最近的数据表明， 侵略和获得优势产生了一种对社会压力有抵抗力的表型， 从属地位的潜在机制产生了一种易受社会压力影响的表型， 一系列不良的行为和生理后果。尽管社会地位 和压力，支配的神经化学机制只受到有限的关注， 男性几乎没有受到女性的关注。这个项目将通过测试一个 综合了叙利亚仓鼠和恒河猴的一系列假设。该项目将严格测试 总体假设，即负责形成和维持的竞争行为， 优势关系由加压素（AVP）和5-羟色胺（5-羟色胺）以截然不同的方式调节。 HT）在男性和女性中。具体地说，我们认为AVP的激活和5-HT的抑制促进了 在雄性中产生显性地位和抗胁迫表型，同时产生从属地位和胁迫表型。 雌性中的易感表型。相比之下，抑制AVP和激活5-HT促进 雌性的优势和抗应激表型，同时产生从属地位和应激 男性易感表型。这些数据将大大扩展我们对性的认识 神经化学机制的差异，定义社会表型，并将提供创新的 促进抵抗社会压力的性别战略。本项目中获得的数据可以 通过指导男性和女性减压的药物治疗， 以及通过强调AVP靶向药物在男性和5-HT中的作用来指导药物开发， 针对女性的药物。