Noradrenergic regulation of maternal anxiety

描述（由申请人提供）：产后早期对新妈妈来说是一个非常苛刻的时期。大多数妇女心理健康，但情绪障碍，如高度焦虑，是常见的。焦虑症如果不治疗，可能会对母亲和婴儿产生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，或其他母亲焦虑加剧的神经基质知之甚少。实验室大鼠是一个很好的模型来检查产后焦虑相关行为的变化，因为它们和大多数女性一样，在产后早期焦虑减少。我们的实验室最近证明，这种变化部分取决于触觉刺激大坝收到他们的垃圾。事实上，阻止哺乳期的雌性接近它们的幼崽只有四个小时，这会增加母鼠的焦虑，就像发情间期的处女一样。我最近进行的实验表明，腹侧床核的终纹（BSTv）是重要的，以维持这种衰减的焦虑在允许与他们的幼崽接触的母鼠。BSTv在神经化学上是独特的，因为它包含大脑中的一种去甲肾上腺素能神经支配。因此，拟议的实验将检查哺乳期雌性大鼠BSTv内去甲肾上腺素的焦虑相关作用。第一个具体目标将确定在暴露于致焦虑试验之前，直接输注到BSTv中的去甲肾上腺素能激动剂或拮抗剂是否会改变允许或不允许接触其幼崽的雌性动物的焦虑相关行为。第二，在母鼠与其幼崽分离之前和之后，将用微透析监测BSTv内的去甲肾上腺素水平。最后，第三个具体目标将使用三重标记免疫组织化学，以确定是否调制GABA能神经元内的BSTv项目的腹尾侧导水管周围灰质（cPAGv）暴露于焦虑刺激。cPAGv是焦虑相关行为的“最终共同途径”，可能需要通过BSTv抑制以减少焦虑相关行为。这些特定的目标将决定：1）改变BSTv内的去甲肾上腺素是否会影响焦虑，2）去甲肾上腺素水平是否会因与幼崽接触而发生变化，以及3）BSTv是否会调节大脑中更大的恐惧回路。从这些实验中获得的知识将阐明新妈妈焦虑的神经机制，并提高产后妇女焦虑症的诊断和治疗。

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.