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。 几种啮齿类动物的攻击模型已经被 开发来了解侵略的神经生物学基础， 开发药理学干预的目标。 一个共同的特点， 这些啮齿类动物的攻击性模型是， 往往与攻击性行为呈负相关。 新模式 强烈的，无情的侵略性已经被开发出来， 编码一氧化氮合酶神经亚型的基因 选择性删除 雄性nNOS-/-小鼠表现出持续的攻击性 对其他男性，并持续不断的尝试向野生型（WT） 不动情的雌性 雌性nNOS-/-小鼠不显示升高的激动性 行为在入侵者居民或中立的竞技场测试的侵略。 的 这项研究的目的是检验攻击性行为的性别差异。 nNOS-/-小鼠的行为，并确定血清素在 nNOS-/-小鼠的攻击行为。 有四个具体目标， 建议的研究：（1）使用药理学操作， 7-硝基吲唑（一种特异性nNOS拮抗剂），以证实观察结果 nNOS在介导攻击性方面很重要，（2）确定 性类固醇激素在攻击性行为性别差异中的作用 （3）确定雌性nNOS-/-小鼠是否表现出 相对于WT小鼠增加的母体攻击性，以及（4）确定 5-羟色胺在nNOS-/-动物攻击性介导中的作用。

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.