An Animal Model of Mania

描述（由申请人提供）：也许双相情感障碍最基本的特征——它的循环性——使其成为最难在动物身上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，尽管是以适应性而不是病态的方式。白冠雀就是这样的一种典型，这种鸣禽每年在阿拉斯加和加利福尼亚之间迁徙两次。在春季和秋季，这些鸟经历了深刻的行为转变，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著增加。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，躁狂症患者睡眠结构特征的改变，活动增加，目标导向活动增加，以及内源性季节性循环。我们提出建立迁徙麻雀作为躁狂症的模型有三个具体目的：(1)证实迁徙活动与躁狂症的失眠、活动增加和季节性循环有关；(2)确定睡眠剥夺是否触发或增强迁移活动，类似于躁狂症的睡眠剥夺效应；(3)确定情绪稳定药物是否能阻止或预防迁移性失眠。迁徙麻雀可以为研究双相情感障碍的神经生物学和行为提供一个无与伦比的机会，与现有的模型相比，它有许多显著的优势，包括双相情感障碍患者本身。该模型将具有表面有效性和预测有效性，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.