Sex differences in social stress

描述（由申请人提供）：严重抑郁症影响超过10%的美国人口。有几种治疗方案可供选择，但许多人对治疗，药物或两者都没有反应。尽管人们一致认为神经递质如5-羟色胺很重要，但很明显，导致抑郁的机制比简单的5-羟色胺功能缺陷要复杂得多。抑郁症的一个重要特征是，女性受抑郁症影响的可能性几乎是男性的两倍。焦虑症在女性中也更为普遍。然而，由于各种原因，大多数研究抑郁症相关神经生物学机制的动物模型都集中在雄性身上。事实上，有一个迫切需要的模型系统的发展，其中与抑郁和焦虑的行为可以在两个性别（Wizemann和Pardue 2001）进行研究。慢性轻度应激过程可以应用于雄性和雌性啮齿动物，并且这种范例诱导快感缺乏（对奖励刺激失去兴趣）。然而，一些实验室报告说，难以复制慢性轻度压力对行为的影响。相比之下，社会压力（从属）范式在世界各地的实验室群体中产生了可重复的结果。社会压力会引起明显的行为变化，包括快感缺乏和社交回避（或退缩）的显着增加。社会压力对行为的影响可以通过慢性而非急性的抗抑郁治疗来逆转。这是相关的，因为慢性而非急性抗抑郁药治疗对治疗人类情感障碍有效。绝大多数使用社会压力的研究都集中在男性身上。这是因为在大多数啮齿类动物中，雌性的攻击性是最小的，所以很难利用雌性内部的攻击性来制造社会压力。相比之下，雌性加州小鼠（Peromyscus californicus）具有攻击性，因为雄性和雌性都在捍卫领土。此外，初步数据显示，女性有较大的皮质酮反应比男性在居民入侵者的侵略测试。 对特发性抑郁症的深入了解，我们期望它将对测试机制有用。虽然我们的模型可能无法提供与压力诱发抑郁症相关的假设。本申请提出使用独特的生物学的加州小鼠，以检查性别差异的神经生物学机制，介导的影响，社会压力的情感行为。 公共卫生相关性：情感障碍更容易发生在女性身上，但大多数小鼠模型都集中在男性身上，部分原因是后勤问题。我们建议使用社会应激范式来研究雄性和雌性加州小鼠的社会退缩和快感缺乏。我们将研究社会应激对行为和脑源性神经营养因子表达的影响。

DESCRIPTION (provided by applicant): Major depression affects more than 10 percent of the US population. There are several treatment options available, but many individuals do not respond to therapy, medication or both. Despite agreement that neurotransmitters such as serotonin are important, it is clear that the mechanisms contributing to depression are considerably more complex than a simple deficit of serotonin function. One important feature of depression is that women are almost twice as likely as men to be affected by depression. Anxiety disorders are also more prevalent in women. For a variety of reasons however, most animal models examining neurobiological mechanisms related to depression focus on males. Indeed, there is an urgent need for the development of model systems in which behaviors related to depression and anxiety can be studied in both sexes (Wizemann and Pardue 2001). The chronic mild stress procedure can be applied in both male and female rodents, and this paradigm induces anhedonia (loss of interest in a rewarding stimulus). However, some laboratories have reported difficulty in replicating the effects of chronic mild stress on behavior. In contrast, the social stress (subordination) paradigm produces repeatable results in laboratory groups around the world. Social stress induces pronounced behavioral changes including anhedonia and a marked increase in social avoidance (or withdrawal). The behavioral effects of social stress are reversed by chronic, but not acute, antidepressant treatment. This is relevant because chronic, but not acute antidepressant treatment is effective in treating affective disorders in humans. The overwhelming majority of studies using social stress have focused on males. This is because in most species of rodents, female aggression is minimal, so it is difficult to create social stress using intra-female aggression. In contrast, female California mice (Peromyscus californicus) are aggressive, as males and females defend territories. In addition, preliminary data show that females have larger corticosterone responses than males during resident-intruder aggression tests. Insights into idiopathic depression, we expect it will be useful for testing mechanistic. Although our model may not provide hypotheses related to stress-induced depression. This application proposes to use the unique biology of the California mouse to examine sex differences in neurobiological mechanisms that mediate the effects of social stress on affective behaviors. PUBLIC HEALTH RELEVANCE: Affective disorders are more likely to occur in women, yet most mouse models focus on males in part due to logistical issues. We propose to use the social stress paradigm to examine social withdrawal and anhedonia in male and female California mice. We will examine the effects of social stress on behavior and expression of brain derived neurotrophic factor.