Oxytocin signaling is well known to positively influence maternal caregiving behaviors. Therefore, oxytocin receptor (OTR) expression has been characterized in many sites of the brain across female reproductive states. However, almost all characterization of OTRs across reproduction has focused on forebrain sites, even though there are known OTRs in the midbrain dorsal raphe (DR) and periaqueductal gray (PAG) (i.e., the dorsomedial tegmentum). Ignoring these sites is surprising, given that these sites are part of the neurobiological network underlying postpartum behaviors (see background review in Chapter One). To begin to understand the role of OTRs in the dorsomedial tegmentum on postpartum behavior, the experiments in Chapter Two of this dissertation measured autoradiographic binding of the selective OTR antagonist, d(CH2)5–8-ornithine-vasotocin, across four different female reproductive states, diestrous virgins (DV), pregnancy day 10, day of parturition, and postpartum day 7 (PPD 7). OTR binding in the rostral DR and the lateral PAG were higher in recently-parturient dams compared to DV females, but these levels were returned to DV levels by PPD 7. Additionally, there was increased oxytocin-immunoreactive (ir) fiber length in the DR and PAGvl in PPD 7 dams compared to either DV or recently-parturient dams. Given the heterogenous populations of cells in the DR, expression of OTRs on three of the most abundant neuronal phenotypes in the DR, serotonin, dopamine, and GABA, were analyzed in groups of DV and recently-parturient dams. There were more dopaminergic and serotonergic neurons containing OTR immunoreactivity in the rostral DR of recently- parturient dams compared to DV, whereas the number of glutamic acid decarboxylase-OTR colocalized cells was lower in the rostral DR of recently-parturient dams compared to DV. Overall, these data suggest that specific regions of the midbrain PAG are more sensitive to oxytocin signaling around parturition, with dopaminergic and serotonergic neurons accounting for some of that increased sensitivity. Given these changes in dorsomedial tegmentum OTR expression across the early postpartum period, their potential role in postpartum socioemotional behaviors was directly examined. An adeno-associated virus promoting the expression of shRNA against OTR mRNA was created to establish a long-term knock down of OTR expression in the dorsomedial tegmentum (Chapter Three). On pregnancy day 8, females received site-specific infusion of either OTR shRNA vector or a scrambled control vector. Following parturition, dams’ socioemotional behaviors (i.e. caregiving, aggressive, anxiety-like, and depressive-like behaviors) were observed. OTR knockdown (OTRKD) in the dorsomedial tegmentum lead to higher rates of infanticide, less kyphotic nursing (i.e., nursing in an upright erect posture), and more non-pup directed behaviors. There were no effects of OTRKD on dams’ retrieval performance. OTRKD in the dorsomedial tegmentum also increased postpartum aggression, decreased postpartum anxiety, and increased depressive-like behaviors. Finally, OTRKD in the dorsomedial tegmentum decreased serotonin-ir fiber length in the primary somatosensory cortex (S1). Overall, OTR expression in the dorsomedial tegmentum is sensitive to female reproductive state and modifies numerous postpartum behaviors. It may do so by affecting the S1 plasticity necessary to optimize maternal tactile sensitivity to offspring (discussed in Chapter Four).
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