Mothers separated from their newborn infants.
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Ingestion by rats of rat placenta or amniotic fluid enhances opioid-mediated, or partly opioid-mediated, antinociception produced by morphine injection, vaginal or cervical stimulation, late pregnancy, and foot shock. This phenomenon is believed to be produced by a placental opioid-enhancing factor (POEF). Ingestion by rats of human or dolphin placenta has also been shown to enhance opioid antinociception, suggesting that POEF may be common to many mammalian species. We tested bovine amniotic fluid (BAF) for its capacity to enhance morphine antinociception in female Long-Evans rats, as determined by percentage change from baseline tail-flick latency in response to radiant heat, and we report that 0.50 mL BAF effectively enhanced morphine antinociception but did not by itself produce antinociception. The efficacy of POEF across species suggests that POEF may have been functionally (and structurally) conserved during evolution. Furthermore, the availability of POEF at parturition, as well as its ability to enhance pregnancy-mediated antinociception without disrupting maternal behavior, offers a tenable explanation for the long-debated ultimate causality of placentophagia.
C57BL/6J (B6) and DBA/2J (D2) mice differ in maternal behavior and nest building, but previous observations on nest building appear to be contradictory. Lactating B6 females spent more time nest building than lactating D2 females [Physiol. Behav. 67 (1999) 599.]; however, pregnant D2 females have been reported to build better nests than pregnant B6 females [Physiol. Behav. 29 (1982) 153.]. To resolve this apparent discrepancy, virgin B6 and D2 females were mated, and the nest quality of nulligravid, primigravid and lactating primiparous females was compared between groups and with that of virgin females. There were no strain differences in the nest ratings of virgin or mated nulligravid females, nor did these groups differ within strains. Pregnant and lactating females of both strains built better nests than nonpregnant females. There was an increase in nest ratings in both strains on the day of parturition. The nest ratings of pregnant and lactating females were higher in B6 than D2 females. The largest strain differences were observed between pregnant B6 and D2 females. One hypothesis to account for these results is that females of these two strains differ in their levels of or sensitivity to hormones during pregnancy and parturition.
There is a considerable literature on the neurobiology of reward, based largely on studies of addiction or substance abuse. This review considers the possibility that the neural circuits that mediate reward evolved for ethologically relevant cues, such as social attachment. Specifically, mesocorticolimbic dopamine appears important for maternal behavior in rats and pair bonding in monogamous voles. It is not yet clear that dopamine in this pathway mediates the hedonic properties of social bond formation or whether dopamine's role is more relevant to developing associative networks or assigning salience to social stimuli. The neuropeptides oxytocin (OT) and vasopressin (AVP) appear to be critical for linking social signals to the mesocorticolimbic circuit.
The objective of this experiment was to test the hypothesis that early environmental influences could affect cardiovascular reactivity to acute stress in borderline hypertensive rats. This study utilized a cross-fostering paradigm in which borderline hypertensive rat (BHR) pups were reared by their natural spontaneously hypertensive rat (SHR) mothers, by an adoptive SHR dam, or by an adoptive Wistar-Kyoto female. Several maternal behavior measures were taken throughout weaning. Cardiovascular responses to acute stress were measured in adult BHR offspring. SHR dams spent significantly more time engaged in arched, as contrasted with passive, nursing behaviors throughout the preweaning period. Although strain of dam had no effect on resting blood pressure or heart rate, BHR reared by WKY dams had a greatly reduced blood pressure response to acute stress compared with BHR raised by either natural or adoptive SHR dams. These results suggest that the expression of cardiovascular characteristics in the BHR can be modified by early environmental influences and support the hypothesis that the expression of the hypertensive phenotype in the BHR is dependent upon information that is conveyed both genetically and environmentally.
Oxytocin is an important modulator of female reproductive functions including parturition, lactation and maternal behavior, while vasopressin regulates water balance and acts as a neurotransmitter. For decades, it has been suggested that estrogen regulates the production and/or release of oxytocin and vasopressin in the rodent brain. Although several studies demonstrated that estrogen can modulate vasopressin mRNA levels in regions known to contain estrogen receptor (ER), such as the bed nucleus of the stria terminalis and medial amygdala, data from the paraventricular and supraoptic nuclei were inconclusive. Since early immunohistochemical and in situ hybridization studies revealed few, if any, ER containing cells in these hypothalamic nuclei, it was thought that oxytocin and vasopressin were not directly regulated by estrogen. The discovery of a second ER (ER-beta) in the late 1990s suggested that estrogen could act in many brain regions heretofore not considered targets for estrogen action. Initial in situ hybridization studies revealed a wide distribution of ER-beta mRNA in the rat brain including neurons of the supraoptic nucleus and the parvocellular and magnocellular divisions of the paraventricular nucleus. Subsequent double-label in situ hybridization/immunocytochemistry studies showed that ER-beta mRNA was present in oxytocin and vasopressin neurons, with the degree of colocalization being both neuropeptide and region specific. In an attempt to demonstrate that ER-beta mRNA was translated into a biologically active protein, a series of in vivo binding studies were conducted in rats with 125I-estrogen. These data revealed the presence of nuclear estrogen binding sites in neurons of the magnocellular system indicating that ER-beta mRNA was translated into protein. Concurrent studies in mice found that the distribution of ER-beta mRNA and 125I-estrogen binding was similar to rats, although there were some notable differences. For example, ER-beta mRNA and binding were not detected in the mouse supraoptic nucleus and although ER-beta was the principle ER in the paraventricular nucleus, ER-alpha was also present. The prevalence of ERs in the mouse paraventricular nucleus was further investigated using ER-alpha and ER-beta knockout mice for in vivo binding studies with 125I-estrogen. The results of these studies showed that ER-beta was the predominant ER in the paraventricular nucleus and confirmed the presence of ER-beta in other brain regions. Moreover, our group recently generated and characterized several polyclonal antisera raised against the C-terminus of ER-beta. Through the use of these antisera, we have confirmed the presence of ER-beta in the rat paraventricular and supraoptic nuclei and shown that ER-beta is colocalized, in part, with oxytocin and vasopressin. To assess the ability of estrogen to modulate the expression of oxytocin mRNA, ovariectomized rats were treated with vehicle or estradiol and the brains processed for in situ hybridization. The results of these studies revealed that estradiol down-regulated oxytocin mRNA in the rat paraventricular nucleus within 6 h of treatment. Together these data and the observation that some of the oxytocin and vasopressin neurons contain ER-beta suggest that estrogen, acting through ER-beta, may directly regulate oxytocin gene expression. However, since the paraventricular nucleus has many subdivisions with different projections and the degree of colocalization of ER-beta with oxytocin/vasopressin varies among subdivisions, the effects of estrogen treatment on gene expression requires further study to ascertain the role of estrogen action in this neuronal systems.
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Two major consequences of placentophagia, the ingestion of afterbirth materials that occurs usually during mammalian parturition, have been uncovered in the past several years. The first is that increased contact, associated with ingesting placenta and amniotic fluid from the surface of the young, causes an accelerated onset of maternal behavior toward those young. The second, which probably has importance for a broader range of mammalian taxa than the first, is that ingestion of afterbirth materials produces enhancement of ongoing opioid-mediated analgesia. The active substance in placenta and amniotic fluid has been named POEF, for Placental Opioid-Enhancing Factor. Recent research on both consequences is summarized, with particular attention to POEF, the generalizability of the enhancement phenomenon, its locus and mode of action, and its significance for new approaches to the management of pain and addiction.
Two experiments investigated discrimination learning with preweanling rats (Rattus norvegicus) following different experimental deprivation treatments. In Experiment 1, 10- to 11-day-old Sprague-Dawley rats were deprived for 24 h of either nutrients and maternal contact through placement in an incubator or only nutrients by placement in the nest of a bromocryptine mesylate-treated dam. Bromocryptine mesylate inhibits prolactin release and thereby prevents lactation with only minimal effect on maternal behaviors. After the deprivation period, pups were trained to perform a spatial discrimination for milk infusion into the oral cavity or for the opportunity to suckle the dry nipples of an anesthetized dam. The results revealed, irrespective of deprivation treatment, that pups failed to acquire a simple T-maze spatial discrimination for milk reward although they rapidly learned to approach and locate an anesthetized dam to suckle. Experiment 2 followed up with a different procedure. Results indicated that during bouts of suckling rat pups preferred an active, lactating dam letting down milk to an identical dam not letting down milk due to her pretreatment with bromocryptine mesylate. These results illustrate a constraint on learning which affects immature rats. The capability to learn on appetitively motivated spatial discrimination appears intricately tied to the context in which training occurs. Results are discussed according to how the organism's expectancy can mediate performance.
Anosmia was produced in two female and three male wolves by transection of the olfactory peduncle and was confirmed by their inability to detect meat, urine, feces, anal-gland secretions, and fish emulsion. All operated animals continued to investigate the environment with their noses, to interact normally with other pack members, and to feed at levels which maintained presurgical body weights. No effect was found on reproductive physiology (females: estradiol or progesterone concentrations, ovulation, pregnancy or parturition; males: testosterone, testicular recrudescence or sperm numbers, motility or maturation). One anosmic female became dominant and although she urine-marked with a flexed leg, the rate was lower than typical for dominant females and perhaps contributed to her failure to pair-bond with the dominant male. One anosmic male raised-leg-urinated while competing for pack dominance and when kenneled away from other males. Precopulatory, copulatory, and maternal behavior were observed for one anosmic female and appeared normal. However, neither male that was sexually naive before surgery showed interest in proestrous or estrous females. The possibility that secondary degeneration of brain regions mediating sexual behavior was responsible for the failure of these males to respond was not supported. Not only was the lack of male sexual response the only serious deficit following transection, but the male which was sexually experienced prior to surgery did copulate successfully during his second postoperative breeding season despite continued anosmia. Chemosensory priming from female urine during the protracted proestrous phase, as well as urinary and vaginal odors during estrus, appear to be critical for induction of full sexual potency in sexually naive males. The importance of urine and vaginal secretions in the sexual response of experienced males is uncertain.
Estrogen and progesterone, long considered for their roles as primary hormones in reproductive and maternal behavior, are now being studied as neuroprotective and neuroregenerative agents in stroke and traumatic brain injuries. Collectively, the hormones reduce the consequences of the injury cascade by enhancing anti-oxidant mechanisms, reducing excitotoxicity (altering glutamate receptor activity, reducing immune inflammation, providing neurotrophic support, stimulating axonal remyelinization), and enhancing synaptogenesis and dendritic arborization. Estrogen seems more effective as a prophylactic treatment in females at risk for cardiac and ischemic brain injury, whereas progesterone appears to be more helpful in the post-injury treatment of both male and female subjects with acute traumatic brain damage. However, a recent clinical trial with estradiol replacement therapy in elderly women that have a history of cerebrovascular disease, showed that this hormone was unable to protect against reoccurrence of ischemia or to reduce the incidence of mortality compared to a placebo.
Medial preoptic area (MPA), supraoptic nucleus (SON), magnocellular (MaPVN) and parvocellular (PaPVN) paraventricular hypothalamic nuclei, and mesencephalic lateral tegmentum (MLT) are involved in maternal behavior, parturition and lactation. This study investigated the FosB and Fos immunoreactivity in these regions of virgin, pregnant, parturient, lactating, and lactating-arrested rats. The patterns of FosB and Fos expression were compared between the sections taken from the same animals. Quantitative immunohistochemistry revealed a significant increase in the numbers of FosB-positive neurons in the MPA, SON, MaPVN, and MLT of parturient and lactating females as compared with pregnant or virgin animals. In lactating rats, the numbers of FosB-positive neurons in the MPA, PaPVN, and MLT were increased, but the numbers in the SON and MaPVN were decreased as compared with parturient females. Many Fos-positive neurons were also seen in parturient and lactating rats, and the patterns of Fos expression in each region were quite similar to those of FosB. Moreover, double-labeling immunohistochemistry revealed that: (1) many FosB-positive nuclei were observed in oxytocin and vasopressin neurons of the SON and PVN in parturient rats; (2) within FosB-positive neurons, 89.5% in the MPA, 86.8% in the MLT of parturient rats, and 92% in the MPA and 90.8% in the MLT of lactating animals were also Fos-positive. Only a small number of FosB and Fos-positive neurons were seen in females that were killed in the early stage of parturition. Removal of the litters immediately after parturition completely eliminated FosB and Fos expression in each region in the dams. Taken together, the present results suggest that FosB expression is co-involved with Fos in the neural activation during parturition and lactation in rats.
Prolactin plays a large role in the onset of maternal behavior at parturition. Knowledge of the change in expression of the prolactin receptor in the brain across pregnancy and lactation, however, is limited. Prolactin receptor gene expression was determined by in situ hybridization histochemistry during pregnancy and lactation in rats. Expression of the mRNA for the longform of the prolactin receptor (PRL-R-L) was measured in various forebrain structures in primigravid rats at different stages of pregnancy, in primiparous rats during early, mid-, and late lactation, and in age-matched, nulliparous females in diestrus. Hybridizations were performed using a [33P]-labeled riboprobe specific for the long form of the prolactin receptor mRNA complimentary to 290 bp of the prolactin receptor gene. The following areas of the forebrain were examined: medial preoptic area (MPOA), median preoptic nucleus both dorsal (MePOd) and ventral (MePOv) to the anterior commissure, ventral lateral septum (LSv), and the ventral and principal parts of the bed nucleus of the stria terminalis (BnSTv and BnSTpr, respectively). Overall, the number of cells expressing PRL-R-L mRNA was significantly higher at 2 h postpartum compared to diestrus in all areas examined except the LSv. In addition, there were lower numbers of PRL-R-L cells during all stages of lactation compared to pregnancy. The number of grains per cell in the MPOA and LSv did not change as dramatically as the number of cells expressing PRL-R-L mRNA in those brain regions. These data contribute to the growing body of evidence that the neural lactogenic system changes as a function of female reproductive state. Changes in PRL-R-L mRNA in terms of behavior and endocrine functions are discussed.
This study explored pregnant women's assessment of the health risks associated with maternal smoking. The aim was to determine if stage of change relating to smoking is associated with risk assessment. A cross-sectional survey (employing a self-completion questionnaire) was conducted of all women who attended antenatal clinics at Leicester Royal Infirmary, National Health Service Trust, UK over a 2 week period. Questionnaires were completed by 254 respondents. Twenty seven percent of non-smokers agreed with more than 75% of a series of statements about the dangers of maternal smoking compared to 5% of smokers and 44% of women in social class I (highest social class) agreed with more than 75% of the statements compared with only 10% of women in social classes IV and V (lower social class groups). Married women were twice as likely to concur with more than 75% of the health risks compared to single or cohabiting women and 29% of women intending to breastfeed agreed with more than 75% of the statements compared with only 8.7% of women not intending to breastfeed. There was no significant effect of age, whether the pregnancy was planned, previous obstetric complications or whether the woman had a child with asthma or respiratory infections. A multiple regression analysis indicated that smokers were much less likely to agree with the health risks than their non-smoking counterparts (p = 0.034). Stage of change was related to both the number of health risks agreed with and the level of conviction. A woman's stage of change could be assessed at the start of antenatal care so that appropriate smoking cessation advice can be offered.
Neonatal handling has pervasive effects on the rat brain leading to increased ability to cope with and adapt to stressful stimuli. We determined the effects of neonatal handling on the dopaminergic and serotonergic system, in the male and female rat brain, under basal conditions before and after puberty and after short- and long-term forced swimming stress. Exposure of animals to neonatal handling resulted in sex-dependent changes in the concentration and turnover of monoamines in the different brain areas. In the prepubertal brain, the effect of neonatal handling was manifested as an increase in dopamine turnover in the females, particularly in the hypothalamus, an increase in serotonin levels and a decrease in its turnover in all three brain regions examined of both males and females. Certain of the handling-induced effects observed in the prepubertal brain were reversed in the postpubertal animals. Thus, in the postpubertal brain, the handling-induced changes in serotonin levels and its turnover observed in both sexes before puberty were abolished. On the other hand, the handling-induced increase in hypothalamic dopamine turnover was maintained. After exposure to short-term stress, the effect of handling was manifested on one hand as decreased striatal dopamine levels in the females, and decreased dopamine turnover in the hypothalamus of both males and females, and on the other, as increased serotonin levels in the hypothalamus. After exposure to long-term stress, handled females had decreased dopamine turnover in the hypothalamus and the striatum, but there was no effect of handling on the serotonergic system. Our results provide some neurobiological evidence supporting the determinant role of the mother-infant relationship in the development of psychopathology. Neonatal handling, which modifies normal mother-pup interactions, results in alterations in brain dopaminergic and serotonergic systems, both of which are involved in the etiopathogenesis of major psychoses. Exposure to either short- or long-term stress in adult life results in sex-dependent changes in brain monoamines, which are affected by handling thus making coping more efficient and rendering the stressful stimulus less noxious.
BACKGROUND: The birth of a very premature infant is a critical event in the life of a family and studies have shown that mothers of these infants are at greater risk of psychological distress than mothers of full-term infants. STUDY DESIGN: A total population study of mothers of preterm infants born at less than 32-week gestation at a tertiary referral hospital. SUBJECTS AND METHODS: Sixty-two mothers of very preterm infants (<32 weeks) participated in the present study which examines correlates of maternal depressive symptomatology at 1 month following very premature birth. Information was obtained from structured questionnaires completed by mothers at 1 month after infant admission to neonatal intensive care. RESULTS: Forty percent of the mothers reported significant depressive symptoms on the Edinburgh Postpartum Depression Scale (EPDS). Logistic regression analysis indicated that high maternal stress resulted in an increased likelihood of depressive symptoms (OR 1.15, CI 1.04-1.26, p<0.01). Higher levels of maternal education (p<0.05), and increased perception of support from nursing staff (OR 1.06, CI 0.88-1.00, p<0.05) resulted in decreased likelihood of depressive symptoms. CONCLUSIONS: The birth and subsequent hospitalisation of a very premature infant evokes considerable psychological distress in mothers. These results have implications for policy development in order to enhance family centred care in the neonatal intensive care.
BACKGROUND: The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend that screening for physical abuse during prenatal care visits becomes routine. Although prenatal care visits offer a unique intervention opportunity, screening is not yet standard practice. DATA AND METHODS: We used data from the 1996 and 1997 Pregnancy Risk Assessment Monitoring System (PRAMS) to assess the prevalence of and the factors associated with health care providers' discussion of physical abuse with pregnant women in 14 states. PRAMS is a state-specific, population-based surveillance system that collects information from women on maternal behaviors before and during pregnancy, and at 2 to 6 months postpartum. RESULTS: Between 22% and 39% of the women surveyed reported that health care providers talked with them about physical abuse during prenatal care visits. Health care providers were more likely to discuss physical abuse with women who were black, Hispanic, young (aged <20 and 20 to 29), had a high school education or less, or paid for prenatal care with Medicaid. CONCLUSIONS: Our results indicate that most pregnant women do not report that their prenatal care providers discussed physical abuse with them. Logistic regression analyses identified consistent associations across the 14 states between discussion of abuse and demographic and pregnancy-related factors. A better understanding of the factors associated with whether a health care provider discusses physical abuse with a pregnant woman could increase intervention opportunities.
BACKGROUND: More than 460,000 preterm babies are born annually in the United States, with rates varying depending on the mother's race/ethnicity. Preliminary evidence suggests that the general public may have a lack of knowledge and misconceptions about preterm birth. METHODS: A national telephone survey of U.S. adults, over-sampling for black and Hispanic women, was conducted in 2002 to assess people's knowledge, attitudes, and beliefs related to preterm birth (N=1967). Analyses included racial/ethnic differences among women's responses and comparisons to men's responses. RESULTS: Prematurity was named by <1% of women as the most important issue facing pregnant women and infants. Overall, 34% of women and 31% of men felt that prematurity is a common problem in the United States, and 38% of women and 25% of men believed prematurity to be a serious problem in the United States. More black and Hispanic women considered prematurity to be common and serious. A majority of women (65%) and men (59%) attributed preterm births to risky prenatal maternal behaviors. CONCLUSIONS: Although nearly one in eight babies is born prematurely, most U.S. adults do not consider prematurity to be a serious public health problem. While the etiology can be identified in only half of spontaneous preterm births, the public largely blames the mother's prenatal behavior. Misperceptions are prevalent and may impede future research and prevention efforts if not corrected.