NEURONAL NITRIC OXIDE SYNTHASE AND AGGRESSION

描述(申请人摘要)：不受控制的攻击行为是一种 严重的社会问题。几种具有攻击性的啮齿动物模型 用来理解攻击性的神经生物学基础 开发药理干预措施的目标。的一个共同特征 这些啮齿动物的攻击性模型是大脑中5-羟色胺的浓度 往往与攻击性行为呈负相关。一种新的模式 强烈的、无情的攻击性是利用具有 神经元型一氧化氮合酶(NNOS)基因 有选择地删除。雄性nNOS-/-小鼠表现出持续的攻击性 攻击其他雄性，并不断增加对野生型(WT)的尝试 没有性欲的雌性。雌性nNOS-/-小鼠没有表现出激动性升高 入侵者常驻或中立的攻击测试中的行为。这个 这项研究的目的是检验攻击性的性别差异。 NNOS-/-小鼠行为学变化及5-羟色胺对小鼠行为的影响 NNOS-/-小鼠的攻击行为。该计划有四个具体目标 建议的研究：(1)使用药理手法， 7-硝基吲唑(一种特异性的nNOS拮抗剂)，以证实观察结果 NNOS在调节攻击性方面很重要，(2)确定 性激素在攻击性性别差异中的作用 NNOS-/-小鼠的行为，(3)确定雌性nNOS-/-小鼠是否表现出 与WT小鼠相比，增加了母亲的攻击性，以及(4)确定 5-羟色胺在nNOS-/-动物攻击行为中的中介作用

DESCRIPTION (applicant's abstract): Uncontrolled aggressive behavior is a serious social problem. Several rodent models of aggression have been developed to understand the neurobiological bases of aggression with the goal of developing pharmacological interventions. One common feature of these rodent models of aggression is that brain serotonin concentrations tend to be inversely correlated with aggressive behavior. A new model of intense, unrelenting aggression has been developed using mice that have the gene encoding the neuronal isoform of nitric oxide synthase (nNOS) selectively deleted. Male nNOS-/- mice display persistent aggression against other males, and persistent mounting attempts toward wild-type (WT) anestrous females. Female nNOS-/- mice do not display elevated agonistic behaviors in intruder-resident or neutral arena tests of aggression. The goal of the proposed studies is to examine the sex difference in aggressive behavior of nNOS-/- mice, and to determine the contribution of serotonin in aggressive behavior of nNOS-/- mice. There are four specific aims of the proposed studies: (1) to use a pharmacological manipulation, 7-nitroindazole (a specific nNOS antagonist), to confirm the observation that nNOS is important in mediating aggression, (2) to determine the contribution of sex steroid hormones to the sex difference in aggressive behavior among nNOS-/- mice, (3) to establish if female nNOS-/- mice display increased maternal aggression relative to WT mice, and (4) to determine the role of serotonin in the mediation of aggression in nNOS-/- animals.