Neural Analysis of Maternal Aggression in Rodents

啮齿类动物母性攻击行为的神经分析

• 批准号: 6768835
• 负责人: Stephen Coull Gammie
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6768835
• 关键词: aggression; anxiety; behavior test; behavioral genetics; brain mapping; corticotropin releasing factor; ethology; fear; fos protein; genetically modified animals; genotype; hormone regulation /control mechanism; immunocytochemistry; instinct; laboratory mouse; lactation; maternal behavior; neuropharmacology; neuropsychology; psychopharmacology; social behavior

DESCRIPTION (provided by applicant): To help understand and mitigate human aggression, it is critical to develop appropriate animal models to understand all the different forms of aggression. Maternal aggression is a fierce aggression exhibited towards intruders by lactating female rodents when they are protecting their pups, that may share similarities with other short-lived, but fierce forms of human aggression. The goal of this proposed research, submitted by a new investigator, is to examine the neural basis of maternal aggression in mice. During lactation, decreases in corticotropin releasing hormone (CRH) neurotransmission have been linked to decreases in fear and anxiety. Because maternal aggression is high when fear and anxiety are low, it is possible that decreases in fear are necessary for a dam to be able to attack a normally fear evoking stimulus. Despite a possible link to maternal aggression, no work has systematically examined whether, or how, CRH plays a role in the control of this important social behavior. The studies proposed here test the hypothesis that regulation of CRH during lactation plays a necessary role in switching on maternal aggression. Consistent with this hypothesis we have collected evidence that intracerebroventricular (icv) injections of CRH inhibit maternal aggression and that decreases in endogenous CRH due to developmental intervention increase levels of maternal aggression. The three studies of this proposal will extend these preliminary findings and use multiple approaches to investigate further the role of CRH in maternal aggression. 1) Conduct icv injections of CRH, and a related peptide, urocortin III, and two CRH receptor antagonists to the lateral ventricle to determine the effect on maternal aggression. 2) Examine whether and where levels of CRH mRNA are decreased in mice that exhibit increased levels of maternal aggression due to a developmental intervention. 3) Examine levels of maternal aggression in mice that are missing either the CRH receptor 1 gene, or the CRH receptor 2 gene relative to control mice. Each study will also use indirect markers for neuronal activity, cFOS and FosB, to identify brain regions where CRH may be interacting with maternal aggression circuitry. Many studies have focused on male aggression, but far less is known about the neural basis of female aggression and preliminary results indicate that CRH has the opposite effect on male and maternal aggression. Basic research into sex differences in aggression, then, is important to understanding the biological underpinnings of sex and gender differences in social behavior, health, and disease.

描述（由申请人提供）：为了帮助理解和减轻人类的侵略，至关重要的是开发适当的动物模型以了解所有不同形式的侵略。孕产妇的侵略是一种激烈的侵略，在保护幼犬时通过哺乳啮齿动物哺乳，这可能与其他短暂但凶猛的人类侵略形式具有相似之处。这项拟议研究的目的是由新研究者提交的，是检查小鼠孕产妇侵略的神经基础。在泌乳过程中，皮质激素释放激素（CRH）神经传递的减少与恐惧和焦虑的减少有关。因为当恐惧和焦虑症较低时，孕产妇的侵略性很高，因此恐惧的减少是必要的，使大坝能够攻击通常恐惧的刺激。尽管可能与孕产妇的侵略有联系，但没有系统地检查CRH是否或如何在控制这一重要社会行为的控制中发挥作用。这里提出的研究检验了以下假设：泌乳过程中CRH的调节在开发母体侵略中起着必要的作用。与这一假设一致，我们收集了证据表明，脑室内（ICV）注射CRH会抑制母体攻击，并且由于发育干预而导致的内源性CRH降低，增加了母体侵略的水平。该提案的三项研究将扩展这些初步发现，并使用多种方法进一步研究CRH在母体侵略中的作用。 1）对CRH的ICV注射和相关的肽，尿科素III和两个CRH受体拮抗剂对侧心室进行，以确定对母体侵略的影响。 2）检查小鼠中CRH mRNA的水平是否降低，由于发育干预而表现出孕产妇侵略水平的升高。 3）检查缺少CRH受体1基因或CRH受体2基因相对于对照小鼠的小鼠的母体侵略水平。每项研究还将使用间接标记来进行神经元活动，CFOS和FOSB，以识别CRH可能与母体侵略回路相互作用的大脑区域。许多研究集中在男性侵略上，但对女性侵略的神经基础的了解少得多，初步结果表明，CRH对男性和母体侵略具有相反的影响。因此，侵略性差异的基础研究对于理解社会行为，健康和疾病中性别差异的生物学基础很重要。