An Animal Model of Mania

描述（由申请人提供）：也许双相情感障碍的最基本特征-其循环性质-使其成为最难以在动物中人工建模的疾病之一。另一种方法是寻找自然发生的模型，这些模型已经显示出双相情感障碍的一系列特征，尽管是以适应性的而不是病理性的方式。其中一个例子是白冠麻雀，一种每年在阿拉斯加和加州之间迁徙两次的鸣禽。在春季和秋季，这些鸟类经历了一个深刻的行为转变，从晚上睡觉（像人类一样）到晚上飞行，这种行为在实验室中可靠地表现为夜间活动的显着增加。我们对这些鸟类的初步研究表明，它们表现出许多与人类躁狂症一致的特征，包括睡眠大大减少，躁狂症患者的睡眠结构特征发生变化，活动增加，目标导向活动增加，以及内源性季节性循环。我们建议建立迁移麻雀作为躁狂症的模型，有三个具体的目的：（1）确认迁移活动模型的失眠，活动增加和季节性循环躁狂症;（2）确定是否睡眠剥夺触发或增强迁移活动，类似于睡眠剥夺在躁狂症的影响;（3）确定情绪稳定药物是否可以停止或预防迁移性失眠。迁徙的麻雀可以提供一个无与伦比的机会来研究双相情感障碍的神经生物学和行为，与目前的模型相比，包括双相情感障碍患者本身。该模型将具有表面和预测有效性，并将允许进行侵入性研究，旨在确定迁移和躁狂症固有的循环分子机制，以及当前和未来的情绪稳定药物。

DESCRIPTION (provided by applicant): Perhaps the most fundamental feature of bipolar disorder-its cycling nature-makes it one of the most difficult to model artificially in animals. Another approach is to search for naturally occurring models that already display a constellation of features of bipolar disorder, albeit in an adaptive rather than pathological manner. One such model is the white-crowned sparrow, Zonotricia leucophrys gambelii, a songbird that migrates twice a year between Alaska and California. In the spring and fall, these birds undergo a profound behavioral shift from sleeping at night (like humans) to flying at night, a behavior that reliably manifests as a marked increase in nocturnal activity in the laboratory. Our preliminary studies of these birds suggest that they show many features consistent with mania in humans, including greatly reduced sleep, changes in sleep architecture characteristic of patients with mania, increased activity, increased goal-directed activity, and endogenous seasonal cycling. We propose to establish the migratory sparrow as a model for mania with three Specific Aims: (1) Confirm that migratory activity models the sleeplessness, increased activity and seasonal cycling of mania; (2) Determine if sleep deprivation triggers or augments migratory activity, similar to sleep deprivation effects in mania; (3) Determine if mood stabilizing drugs can stop or prevent migratory sleeplessness. The migratory sparrow could provide an unparalleled opportunity to study the neurobiology and behavior of bipolar disorder, with a number of significant advantages over present models, including bipolar patients themselves. The model would have both face and predictive validity, and would allow performance of invasive studies aimed at identifying the molecular mechanisms of cycling inherent in migration and mania, as well as current and future mood stabilizing drugs.