Noradrenergic regulation of maternal anxiety

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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.