Sex-dependent effects of social status on the regulation of arginine-vasopressin (AVP) V1a, oxytocin (OT), and serotonin (5-HT) 1A receptor binding and aggression in Syrian hamsters (Mesocricetus auratus).

Dominance status in hamsters is driven by interactions between arginine-vasopressin V1a, oxytocin (OT), and serotonin 1A (5-HT1A) receptors. Activation of V1a and OT receptors in the anterior hypothalamus (AH) increases aggression in males, while decreasing aggression in females. In contrast, activation of 5-HT1A receptors in the AH decreases aggression in males and increases aggression in females. The mechanism underlying these differences is not known. The purpose of this study was to determine if dominance status and sex interact to regulate V1a, OT, and 5-HT1A receptor binding. Same-sex hamsters (N = 47) were paired 12 times across six days in five min sessions. Brains from paired and unpaired (non-social control) hamsters were collected immediately after the last interaction and processed for receptor binding using autoradiography. Differences in V1a, OT, and 5-HT1A receptor binding densities were observed in several brain regions as a function of social status and sex. For example, in the AH, there was an interaction between sex and social status, such that V1a binding in subordinate males was lower than in subordinate females and V1a receptor density in dominant males was higher than in dominant females. There was also an interaction in 5-HT1A receptor binding, such that social pairing increased 5-HT1A binding in the AH of males but decreased 5-HT1A binding in females compared with unpaired controls. These results indicate that dominance status and sex play important roles in shaping the binding profiles of key receptor subtypes across the neural circuitry that regulates social behavior.

Postpartum inhibition of ovarian steroid action increases aspects of maternal caregiving and reduces medial preoptic area progesterone receptor expression in female rats.

The rapid peripartum onset of maternal caregiving involves progesterone synergizing with estradiol, but prolonging progesterone exposure past this time can prevent the emergence of mothering. Interestingly, there is a 7-10day-long rise in progesterone during mid-lactation, but its effects on mothering are unknown. Given progesterone's potential to inhibit mothering onset, this mid-lactational rise may contribute to the normal attenuation of caregiving behaviors across lactation. To evaluate this, recently-parturient rats were ovariectomized and caregiving observed from postpartum days (PPD) 7-18. Ovariectomized dams were found to lick, hover over, and nurse in kyphosis more frequently than controls. Ovariectomy also decreased medial preoptic area (mPOA) progesterone receptor (PR) mRNA, which was negatively correlated with pup licking and kyphosis, but it did not affect mPOA levels of oxytocin receptor or vasopressin V1a receptor mRNAs. In a second study, gonadally intact dams were given the PR antagonist, RU 486, and were found to display more kyphosis and less supine nursing compared to controls. Finally, progesterone sensitivity across lactation was examined by measuring numbers of PR immunoreactive (PR-ir) cells in the mPOA, ventral bed nucleus of the stria terminalis (BSTv) and periaqueductal gray (PAG). PR-ir was higher in the mPOA at parturition compared to virgins, while PR-ir in the mPOA and BSTv dropped from parturition to PPD 7 and remained low through PPD 18. The number of PR-ir cells in the PAG was constant. Thus, in addition to their well-known prepartum effects, ovarian hormones limit the display of some maternal behaviors during mid-to-late lactation and contribute to their decline as weaning approaches.

The effects of perinatal SSRI exposure on anxious behavior and neurobiology in rodent and human offspring.

While the postpartum period is typically associated with increased positive affect, many women will develop a depressive- or anxiety-related disorder during this time, which can degrade the mother-infant bond and lead to detrimental consequences for the infant. Given the potential for negative consequences, effective treatments have been critical, with selective serotonin reuptake inhibitors (SSRIs) being the most commonly-prescribed pharmaceutical agents to treat postpartum depression and anxiety. However, SSRIs can readily cross the placenta and are present in breast milk, so they might, therefore, unintentionally interact with the developing fetus/infant. There is already experimental evidence that perinatal SSRI exposure has a number of long-term effects on offspring, but this review focuses on the current literature examining the timing and consequences of perinatal SSRI exposure specifically on anxiety-like behaviors in rodents and humans, with an emphasis on the anxiety-related brain regions of the amygdala and hippocampus. This review also discusses discrepancies between the rodent and human literatures and how they might inform future studies. Finally, some key factors to consider when examining the role of perinatal SSRIs on offspring anxiety will be discussed, such as the duration of SSRI exposure and the potential neuroprotective effects of SSRIs. Given the extensive prescribing of SSRIs, the potential health consequences of perinatal SSRI exposure, and the discrepancies in the literature, it will be necessary to critically examine the factors underlying offspring anxiety outcomes.

Interaction between postpartum stage and litter age on maternal caregiving and medial preoptic area orexin.

Most maternal caregiving behaviors change across lactation to match the developmental needs of the continuously aging offspring. However, it is mostly unknown whether the dams' postpartum stage or litter age is the primary driving force of these changes. In this study, postnatal day 1 and 8 litters were cross-fostered or in-fostered to postpartum day 1 or 8 dams. Five days later, undisturbed observations of maternal caregiving behaviors were performed on the subsequent two days. We found a main effect of dams' postpartum stage on the frequency that mothers spent with the pups and displayed erect postures over them (hovering over and kyphosis), although it was mostly driven by an interaction between postpartum stage and litter age: early-postpartum dams were in contact with younger litters and in erect postures more often with younger litters compared to later-postpartum dams with younger litters. Additionally, there was an interaction between postpartum stage and litter age on the litter weights because older litters living with later-postpartum dams were heavier than older litters living with early-postpartum dams. There was also an interaction between postpartum stage and litter age on the dams' bodyweight, with early-postpartum dams living with younger litters weighing the least and later-postpartum dams living with younger litters weighing the most. Because activity of the neuropeptide, orexin, within the medial preoptic area (mPOA) has been implicated in maternal nursing and other caregiving behaviors, we measured mPOA levels of orexin-A but it was not affected by postpartum stage or litter age (nor was there an interaction). However, high orexin-A was negatively associated with the frequency of contact with pups and the display of erect postures. These results indicate that changes in caregiving across lactation are driven by endogenous factors in the dams, age-related cues they receive from offspring, and interactions between these factors.