Noradrenergic regulation of maternal anxiety

描述(申请人提供)：产后初期对新妈妈来说是一个要求极高的时期。大多数女性保持心理健康，但情绪障碍，如高度焦虑，很常见。焦虑症如果得不到治疗，可能会对母亲和婴儿产生短期和长期的有害后果。对于大多数新妈妈来说，导致情绪稳定或改善的神经底物，或者对其他妈妈来说焦虑程度上升的神经底物，人们知之甚少。实验室大鼠是检测产后焦虑相关行为变化的极佳模型，因为它们和大多数女性一样，在产后早期经历了焦虑的减少。我们的实验室最近证明，这种变化在一定程度上依赖于水坝从它们的粪便中获得的触觉刺激。事实上，阻止哺乳期雌性幼崽在短短四个小时内接触幼崽会增加母犬的焦虑，而不是处女发情。我最近进行的实验表明，终纹腹侧床核(BSTv)对于维持这种减弱的焦虑很重要，因为它们允许与幼崽接触。BSTv在神经化学上是独一无二的，因为它包含大脑中最密集的去甲肾上腺素能神经之一。因此，拟议的实验将检验去甲肾上腺素在哺乳期雌性大鼠的BSTv中与焦虑相关的影响。第一个具体目标将确定直接注入BSTv的去甲肾上腺素能激动剂或拮抗剂是否会改变雌性幼崽在接受焦虑测试之前的焦虑相关行为。其次，在母鼠与幼崽分离之前和之后，将用微透析法监测BSTv内的去甲肾上腺素水平。最后，第三个特定目的将使用三标记免疫组织化学来确定在暴露于引起焦虑的刺激后，BSTv内的调制GABA能神经元是否投射到尾侧中脑导水管周围灰质(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。这些特定的目标将决定：1)改变BSTv内的去甲肾上腺素是否影响焦虑，2)去甲肾上腺素水平是否因接触幼崽而改变，以及3)BSTv是否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生儿母亲焦虑的神经机制，并加强对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.