Sex Differences in the Social Brain

社交大脑中的性别差异

基本信息

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
项目类别：
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

项目摘要

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.

项目概要在大多数哺乳动物物种中，同一物种个体之间的社会互动受以下因素支配：支配关系。这些等级关系是通过竞争性建立和维持的行为，包括攻击性。重要的是，最近的数据表明，潜在的神经机制攻击性和获得统治地位会产生一种能够抵抗社会压力的表型，而从属地位的机制会产生一种对社会压力敏感的表型，这可能会导致许多不良的行为和生理结果。尽管有社会地位的关系和压力等方面，支配地位背后的神经化学机制只受到了有限的关注。男性几乎没有关注女性。该项目将通过测试使用叙利亚仓鼠和恒河猴整合了一系列假设。该项目将严格测试总体假设是，竞争行为负责形成和维持加压素 (AVP) 和血清素 (5- HT）在男性和女性中。具体来说，我们建议 AVP 的激活和 5-HT 的抑制促进男性的主导地位和抗应激表型，同时产生从属地位和压力女性易感表型。相反，抑制 AVP 和激活 5-HT 可促进女性的主导地位和抗压表型，同时产生从属地位和压力男性易感表型。总之，这些数据将极大地扩展我们对性的了解定义社会表型的神经化学机制的差异将提供创新促进抵抗社会压力的针对性别的战略。本项目获得的数据可以通过指导男性和女性减轻压力的药物治疗，产生几乎立竿见影的临床影响以及通过强调 AVP 靶向药物在男性和 5-HT- 中的作用来指导药物开发女性靶向药物。