Neural Analysis of Maternal Aggression

母亲攻击性的神经分析

基本信息

批准号：
6898812
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
项目类别：
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

项目摘要

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攻击行为，开发适当的动物模型来理解所有不同形式的攻击行为至关重要。母性攻击是哺乳期雌性啮齿类动物在保护幼崽时对入侵者表现出的激烈攻击行为，这可能与人类其他短暂但激烈的攻击形式有相似之处。这项研究由一位新研究者提交，其目标是检查小鼠母性攻击性的神经基础。哺乳期间，促肾上腺皮质激素释放激素 (CRH) 神经传递的减少与恐惧和焦虑的减少有关。因为当恐惧和焦虑较低时，母亲的攻击性较高，因此，有可能，恐惧的减少对于母鼠能够攻击通常引起恐惧的刺激是必要的。尽管 CRH 可能与母亲的攻击行为有关，但还没有任何研究系统地研究 CRH 是否或如何在控制这种重要的社会行为中发挥作用。这里提出的研究检验了以下假设：哺乳期间 CRH 的调节在母亲攻击性的转变中发挥着必要的作用。与这一假设一致，我们收集的证据表明，脑室内（icv）注射 CRH 会抑制母亲的攻击性，并且由于发育干预而导致内源性 CRH 的减少会增加母亲的攻击性水平。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 在母亲攻击行为中的作用。 1) 将 CRH 和相关肽、尿皮质素 III 和两种 CRH 受体拮抗剂进行侧脑室静脉注射，以确定对母体攻击性的影响。 2) 检查由于发育干预而表现出母性攻击性水平增加的小鼠中 CRH mRNA 水平是否以及何处降低。 3) 检查缺失 CRH 受体 1 基因或 CRH 受体 2 基因的小鼠相对于对照小鼠的母体攻击性水平。每项研究还将使用神经元活动的间接标记物 cFOS 和 FosB 来识别 CRH 可能与母体攻击回路相互作用的大脑区域。许多研究都集中在男性攻击性上，但对女性攻击性的神经基础知之甚少，初步结果表明 CRH 对男性和母亲的攻击性具有相反的作用。因此，对攻击行为中性别差异的基础研究对于理解性别的生物学基础以及社会行为、健康和疾病方面的性别差异非常重要。