An Animal Model of Mania

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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.