Sex Differences in the Roles of Oxytocin and Vasopressin in Social Withdrawal

催产素和加压素在社交退缩中的作用的性别差异

基本信息

批准号：
8601632
负责人：
Michael Q. Steinman
金额：
$ 2.51万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-01-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8601632
关键词：
Adrenal Glands Adverse effects Affect Aggressive behavior Amygdaloid structure Anhedonia Animal Model Animals Appearance Argipressin Beds Behavior Behavioral Model Behavioral Symptoms Biological Brain California Cell Nucleus Cells Chronic Citalopram Conflict (Psychology)Consumption Corticosterone Development Diagnostic Drug Targeting Exposure to FOS gene Female Future Growth Human Hypothalamic structure Immunohistochemistry Individual Infusion procedures Intranasal Administration Investigation Label Laboratory Rat Laboratory mice Lateral Maintenance Major Depressive Disorder Mediating Mental Depression Microtus Modeling Mood Disorders Mus Neurons Neuropeptides Outcome Oxytocin Oxytocin Receptor Peromyscus Pharmaceutical Preparations Pharmacologic Substance Physiological Pituitary Gland Plasma Play Population Predisposition Proteins Rattus Regulation Reporting Rewards Rodent Role Sex Characteristics Sexual Dysfunction Sleep Disorders Social Behavior Social Development Social Interaction Sucrose Syndrome System Testing Therapeutic Time Vasopressins Weight Gain Withdrawal Woman argipressin receptor biological adaptation to stress brain tissue coping depressive symptoms experience human subject hypothalamic-pituitary-adrenal axis improved insight interest lateral ventricle mRNA Expression male men monoamine novel paraventricular nucleus receptor research study response sex social social stress stressor supraoptic nucleus treatment strategy

项目摘要

Depression occurs in over 10% of the US population each year, and women are reported to experience depression twice as frequently as men. Physiological reactivity to social stressors is evolutionarily conserved and both rodents and humans experience social conflicts that can alter affect and behavior. In animal models social stress induces anhedonia, a loss of interest in previously rewarding activates, which is a major diagnostic feature of depression. Diminished reward can result in reduced consumption of sucrose and reduced time engaging in social interaction. This allows for the study of how changes in the brain are associated with these changes in behavior. Aggressive interactions are infrequent in commonly used laboratory rats and mice, making it difficult or impossible to study effects of social stress on females. California mouse (Peromyscus californicus) males and females are territorial, making them suitable for studying sex differences. Female but not male California mice exposed to social stress spend less time engaging in social interactions. Oxytocin (OT) and arginine vasopressin (AVP) are related neuroproteins that play important roles in social interactions. Both proteins have been identified as potential targets for drugs in the treatment of depression. The proposed study uses three experiments to examine sex differences in how OT and AVP systems in the brain respond to social stress. In the first experiment, triple-label immunohistochemistry will be used on brain tissue acquired from mice exposed to social stress, social interaction, or control conditions. This allows for quantifying the number of OT and AVP neurons that contain c-fos, a protein whose presence suggests that the cells were recently activated. The second experiment will use real time PCR to examine how OT and AVP receptor mRNA expression in the lateral septum, central amygdala, paraventricular nucleus and pituitary is changes 4 wk after social defeat. Finally, in experiment 3, I will infuse OT or OT receptor antagonist into the lateral ventricles just before chronic social stress to determine whether manipulating OT function can block or induce the development of social aversion 4 wk later. Together these experiments should provide insight into whether OT and AVP play a role in the development and expression of social withdrawal.

每年超过 10% 的美国人口患有抑郁症，据报道，女性患抑郁症的频率是男性的两倍。对社会压力源的生理反应在进化上是保守的，啮齿动物和人类都会经历可能改变情感和行为的社会冲突。在动物模型中，社会压力会导致快感缺乏，即对先前的奖励活动失去兴趣，这是抑郁症的一个主要诊断特征。奖励减少会导致蔗糖消耗量减少和参与社交互动的时间减少。这使得我们可以研究大脑的变化如何与这些行为变化相关。在常用的实验室大鼠和小鼠中，攻击性互动很少见，这使得研究社会压力对雌性的影响变得困难或不可能。加州小鼠（Peromyscus californicus）雄性和雌性都有领地意识，这使得它们适合研究性别差异。暴露在社会压力下的雌性而非雄性加州小鼠参与社交互动的时间较少。催产素 (OT) 和精氨酸加压素 (AVP) 是相关的神经蛋白，在社交互动中发挥重要作用。这两种蛋白质已被确定为治疗抑郁症药物的潜在靶点。拟议的研究使用三个实验来检查大脑中的 OT 和 AVP 系统如何应对社会压力的性别差异。在第一个实验中，三标记免疫组织化学将用于从暴露于社会压力、社交互动或控制条件的小鼠获得的脑组织。这可以量化含有 c-fos 的 OT 和 AVP 神经元的数量，c-fos 是一种蛋白质，其存在表明细胞最近被激活。第二个实验将使用实时PCR来检测社交失败后4周后外侧隔膜、杏仁核中央、室旁核和垂体中OT和AVP受体mRNA表达的变化。最后，在实验3中，我将在慢性社交压力之前将OT或OT受体拮抗剂注入侧脑室，以确定操纵OT功能是否可以阻止或诱导4周后社交厌恶的发展。这些实验一起应该可以深入了解 OT 和 AVP 是否在社交退缩的发展和表达中发挥作用。