Variance in sibling mothering received and adult mothering, anxiety and serotonin The long-term objectives of this NRSA proposal are to identify how variance among siblings in maternal care received influences mechanisms related to later sibling differences in: 1) maternal behavior, 2) anxiety-like behaviors, and 3) serotonin synthesis and release. This research is novel and important because in humans and non-human animals, it is well-known that variance in maternal care received greatly differs between families and has tremendous effects on offspring neurological and social development, yet studies examining this phenomenon within families are scarce. Using a rat model, I will examine the association between mother- infant interactions during the early postnatal period and adult mothering, anxiety-related behaviors, and serotonin activity among sisters.
In Specific Aim 1, I will conducted finely detailed observations of maternal care received during the first ten days of life and determine if high-licked females provide more maternal care to their own offspring compared to their low-licked sisters. During adulthood, these females will also be tested on the elevated plus maze (a well-validated measure of anxiety-like behavior in rodents) to determine if differences in anxiety are associated with their differences in mothering.
In Specific Aim 2, I wil use Western Blots to measure expression of tryptophan hydroxylase 2 (TPH2, the major enzyme responsible for brain serotonin synthesis) in the dorsal raphe with the hypothesis that it is upregulated in high-licked females compared to their low-licked sisters. Finally, in Specific Aim 3, I will determine if serotonin release in the ventral bed nucleus of the stria terminalis (BSTv), an area receiving dense serotonergic projections from the DR and associated with maternal behavior and anxiety, is higher in high-licked females than their low-licked sisters. To accomplish this, I will use in vivo microdialysis to measure serotonin release in the BSTv in postpartum sisters while they interact with pups. In a second experiment in this Aim, I will determine if variability among sisters in mothering can be minimized by administration of the 5-HT1a receptor agonist, flesinoxan, to low-licked sisters. In this proposal, I aim to clarify early perinatal predictors of individual differences in anxiety-related and mothering behaviors, which will promote a better understanding of developmental trajectories leading women toward risk for adult anxiety disorders.
1 in 4 American meet the diagnostic criteria for anxiety disorders. To fulfill the missions of NIH, this research will provide a means to predict who is at risk for disorders in adult emotional and postpartum mothering according to differences in early mother-infant interactions and serotonergic systems.
|Ragan, Christina M; Harding, Kaitlyn M; Lonstein, Joseph S (2016) Associations among within-litter differences in early mothering received and later emotional behaviors, mothering, and cortical tryptophan hydroxylase-2 expression in female laboratory rats. Horm Behav 77:62-71|
|Ragan, C M; Lonstein, J S (2014) Differential postpartum sensitivity to the anxiety-modulating effects of offspring contact is associated with innate anxiety and brainstem levels of dopamine beta-hydroxylase in female laboratory rats. Neuroscience 256:433-44|