Noradrenergic regulation of maternal anxiety

描述（申请人提供）：产后早期对新妈妈来说是一个非常苛刻的时期。大多数妇女保持心理健康，但情绪障碍，如高度焦虑，是常见的。焦虑症如果不及时治疗，会对母亲和婴儿造成短期和长期的有害后果。导致大多数新妈妈情绪稳定或改善的神经基质，或导致其他母亲焦虑加剧的神经基质，目前尚不清楚。实验室大鼠是检验产后焦虑相关行为变化的绝佳模型，因为它们和大多数女性一样，在产后早期焦虑有所减少。我们的实验室最近已经证明，这种变化部分取决于从它们的垃圾中获得的触觉刺激。事实上，阻止哺乳期雌性接近它们的幼崽仅仅4个小时，就会使雌性的焦虑程度增加到初生雌鼠的焦虑程度。我最近进行的实验表明，终纹腹床核（BSTv）对于维持与幼崽接触的母鼠的这种减轻的焦虑很重要。BSTv在神经化学上是独一无二的，因为它含有大脑中最密集的去肾上腺素能神经支配之一。因此，拟议的实验将检验在哺乳期雌性大鼠BSTv中去甲肾上腺素的焦虑相关作用。第一个具体目标是确定在暴露于焦虑性测试之前，直接注入BSTv的去甲肾上腺素能激动剂或拮抗剂是否会改变雌性小鼠的焦虑相关行为。其次，在母犬与幼崽分离前后，BSTv内的去甲肾上腺素水平将通过微透析进行监测。最后，第三个特定目标将使用三标记免疫组织化学来确定在暴露于焦虑刺激后，BSTv内的gaba能神经元是否被调节到腹侧尾侧导水管周围灰质（cPAGv）。cPAGv是焦虑相关行为的“最终共同途径”，可能需要被BSTv抑制以减少焦虑相关行为。这些具体的目标将决定：1)改变BSTv内的去甲肾上腺素是否会影响焦虑，2)与幼崽接触后去甲肾上腺素水平是否会改变，以及3)BSTv是否会调节大脑中更大的恐惧回路。通过这些实验获得的知识将阐明新妈妈焦虑的神经机制，提高产后女性焦虑障碍的诊断和治疗。

DESCRIPTION (provided by applicant): The early postpartum period is an extremely demanding time for new mothers. Most women remain psychologically healthy but emotional disorders, such as high anxiety, are common. Anxiety disorders left untreated can have both short and long term detrimental consequences for the mother and infant. The neural substrates leading to stable or improved mood for most new mothers, or elevated anxiety for other mothers, are poorly understood. Laboratory rats are an excellent model to examine postpartum changes in anxiety-related behaviors because they, like most women, experience a decrease in anxiety during the early postpartum period. Our laboratory has recently demonstrated that this change is partially dependent on the tactile stimulation dams receive from their litter. Indeed, preventing lactating females from accessing their pups for as little as four hours increases dams' anxiety to that of diestrus virgins. Recent experiments I conducted suggest that the ventral bed nucleus of the stria terminalis (BSTv) is important for maintaining this attenuated anxiety in dams allowed contact with their pups. The BSTv is neurochemically unique because it contains one of the densest noradrenergic innervations in the brain. The proposed experiments will, thus, examine the anxiety-related effects of norepinephrine within the BSTv of lactating female rats. The first specific aim will determine if noradrenergic agonists or antagonists infused directly into the BSTv alter anxiety-related behaviors in females either allowed access to their pups, or not, before exposure to an anxiogenic test. Second, levels of norepinephrine within the BSTv will be monitored with microdialysis before and after dams are separated from their pups. Finally, the third specific aim will use triple-label immunohistochemistry to determine if modulated GABAergic neurons within the BSTv project to the ventrocaudal periaqueductal gray (cPAGv) after exposure to an anxiogenic stimulus. The cPAGv is a "final common pathway" for anxiety-related behaviors and may need to be inhibited by the BSTv for reduced anxiety-related behaviors. These specific aims will determine: 1) if altering norepinephrine within the BSTv affects anxiety, 2) if norepinephrine levels change as the result of contact with pups, and 3) if the BSTv modulates a larger fear circuitry in the brain. Knowledge gained from these experiments will elucidate the neural mechanisms underlying maternal anxiety in new mothers and enhance the diagnosis and treatment of anxiety disorders in postpartum women.