Noradrenergic alpha-2 receptor modulators in the ventral bed nucleus of the stria terminalis: Effects on anxiety behavior in postpartum and virgin female rats.

2014

Neuroscience

In female mammals, the postpartum period involves dramatic shifts in many socioemotional behaviors. This includes a suppression of anxiety-related behaviors that requires recent physical contact with offspring. Factors contributing to differences among females in their susceptibility to the anxiety-modulating effect of offspring contact are unknown, but could include their innate anxiety and brain monoaminergic activity. Anxiety behavior was assessed in a large group of nulliparous female rats and the least-anxious and most-anxious tertiles were mated. Anxiety was assessed again postpartum after females were permitted or prevented from contacting their offspring 4 h before testing. Levels of dopamine β-hydroxylase (DBH, norepinephrine synthesizing enzyme) and tryptophan hydroxylase- 2 (TPH2, serotonin synthesizing enzyme) were measured in the brainstem and dorsal raphe, respectively. It was found that anxiety-related behavior in the two groups did not differ when dams were permitted contact with offspring before testing. Removal of the offspring before testing, however, differentially affected anxiety based on dams’ innate anxiety. Specifically, dams reverted back to their pre-mating levels of anxiety such that offspring removal slightly increased anxiety in the most-anxious females but greatly lowered anxiety in the least-anxious females. This reduction in anxiety in the least-anxious females after litter removal was associated with lower brainstem DBH. There was no relationship between females’ anxiety and dorsal raphe TPH2. Thus, a primary effect of recent contact with offspring on anxiety-related behavior in postpartum rats is to shift females away from their innate anxiety to a more moderate level of responding. This effect is particularly true for females with the lowest anxiety, may be mediated by central noradrenergic systems, and has implications for their ability to attend to their offspring.

Section: Discussionmentioning

confidence: 77%

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

Ragan

2014

Neuroscience

“…Subjects were female Long-Evans rats born and raised in our breeding colony and maintained as previously described (Smith et al, 2013). Pregnant females were singly housed approximately five days before parturition, and litters culled to contain four males and four females within 24 hours after birth.…”

Section: Methodsmentioning

confidence: 99%

Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe

Holschbach

Psychoneuroendocrinology

2017

Self Cite

The adult brain shows remarkable neuroplasticity in response to hormones and the socioemotional modifications that they influence. In females with reproductive and maternal experience, this neuroplasticity includes the birth and death of new and existing cells in several forebrain regions involved in maternal caregiving and postpartum affective state. Such plasticity in midbrain sites critical for these processes has never been examined, though. Visualizing bromodeoxyuridine (BrdU) to label mitotic cells, l NeuroD for neuronal precursors, and TUNEL to identify dying cells, we found that the midbrain dorsal raphe nucleus (DR, the source of most ascending serotoninergic projections) exhibited significant neuroplasticity in response to motherhood. Specifically, BrdU analyses revealed that DR newborn cell survival (but not proliferation) was regulated by reproductive state, such that cells born early postpartum were less likely to survive compared to cells born during late pregnancy. Many of the surviving cells in the DR were NeuN immunoreactive, suggesting a neuronal phenotype. Similarly, late postpartum rats had fewer NeuroD-immunoreactive DR cells than early postpartum rats. Maternal experience contributed to the late postpartum reduction in DR newborn cell survival because removing the litter at parturition increased cell survival and reduced cell death. Unlike cytogenesis in the maternal hippocampus, which is reduced by circulating glucocorticoids, DR newborn cell survival was unaffected by postpartum adrenalectomy. These effects of reproductive state and motherhood on DR plasticity were associated with concurrent changes in DR levels of serotonin's precursor, 5-HTP, and its metabolite, 5-HIAA. Our results demonstrate for the first time that cytogenesis occurs in the midbrain DR of any adult mammal, that DR plasticity is influenced by female reproductive state and maternal experience, and that this plasticity is accompanied by changes in DR serotonergic function. Because serotonin is critical for postpartum caregiving behaviors and maternal affective state, neuroplastic changes in the DR may contribute to the neurochemical changes necessary for successful motherhood.

“…Lonstein 24 in the mPFC was positively associated with retrieval in nulliparae, but negatively associated with the frequency of licking in the postpartum females. Differences between the female reproductive states in basal mPFC serotonergic activity may help explain the opposite directions of effects, because dams already have higher serotonin metabolism in the cortex and some other brain sites compared to virgins or pregnant females (e.g., Desan et al, 1988;Lonstein, Dominguez, Putnam, Vries, and Hull, 2003;Smith, Piasecki, Weera, Olszewicz, and Lonstein, 2013), so perhaps serotonergic activity in the mPFC that is neither too high nor too low is optimal for maternal responsiveness -lower levels in dams but higher levels in virgins meet in the middle to promote maternal responsiveness in both groups. It should also be recognized that while sensitized and postpartum maternal behaviors appear quite similar, the behaviors do not necessarily emerge via similar neurochemical processes.…”

Section: Accepted Manuscriptmentioning

confidence: 97%

Associations among within-litter differences in early mothering received and later emotional behaviors, mothering, and cortical tryptophan hydroxylase-2 expression in female laboratory rats

Ragan

Harding

2016

Hormones and Behavior

Self Cite

This article is part of a Special Issue "Parental Care". The effects of differential maternal care received on offspring phenotype in rodents has been extensively studied between litters, but the consequences of differential mothering within litters on offspring neurobehavioral development have been rarely examined. We here investigated how variability in maternal care received among female rat siblings (measured four times daily on postnatal days 4, 6, 8, and 10) relates to the siblings' later emotional and maternal behaviors. As previously reported, we found that some female pups received up to three times more maternal licking bouts compared to their sisters; this difference was positively correlated with the pups' body weights. The number of maternal licking bouts that females received was negatively correlated with their later neophobic behaviors in an open field during periadolescence, but positively correlated with their anxiety-related behavior in an elevated plus maze during adulthood. Licking received was also positively correlated with females' later likelihood to retrieve pups in a maternal sensitization paradigm. In addition, females' neophobia during adolescence and anxiety-related behavior during adulthood predicted some aspects of both postpartum and sensitized maternal responsiveness. Medial prefrontal cortex expression of tryptophan hydroxylase-2 (TPH2; enzyme necessary for serotonin synthesis) was negatively associated with early maternal licking received. Interestingly, cortical TPH2 was positively associated with the maternal responsiveness of sensitized virgins but negatively associated with it in postpartum females. These results indicate that within-litter differences in maternal care received is an often neglected, but important, contributor to individual differences in offspring socioemotional behaviors as well as to the cortical serotonin neurochemistry that may influence these behaviors.