Intergenerational effects of cocaine on maternal aggressive behavior and brain oxytocin in rat dams

Gestational cocaine treatment results in significantly increased maternal aggression towards an intruder by postpartum day six, while acute postpartum treatment dose dependently decreases maternal aggressive (MA) behavior. Both increased and decreased aggression in the cocaine-treated dams are correlated with either decreased or increased levels of oxytocin in the amygdala, respectively. The current study was an effort to determine whether the effect of gestational cocaine on maternal aggression is transient or would continue into the postpartum period; whether an intermittent cocaine treatment regimen, which incorporates gestational and postpartum intermittent cocaine treatment, would differ from chronic daily gestational treatment; and finally, whether next generation female offspring of cocaine-treated or control dams would have altered MA behavior and oxytocin system changes attributable to either prenatal drug exposure, rearing condition or both. We now report no increase in maternal aggression following chronic gestational treatment and significantly lower levels of aggression in intermittently treated dams on postpartum day eight, with no significant effects in either group on postpartum day 12. Young adult female offspring of the cocaine-treated and control dams, who reared their own natural litters and were tested on postpartum day eight for maternal aggression, had higher levels of maternal aggression towards an intruder attributable to both prenatal cocaine exposure and rearing condition. Higher aggression in cocaine-reared next generation dams was associated with lower levels of oxytocin in the amygdala. Intergenerational effects of cocaine were apparent with respect to aggression and oxytocin system changes.     

Maternal aggression in mice and rats towards male and female conspecifics

Although postpartum aggression is primarily studied in laboratory mice and rats, it is unclear how the two species compare in terms of the factors associated with peak levels of aggressive behavior. Using the same experimental protocol, we assessed the relative effect of intruder sex and time since parturition on the frequency of maternal aggression in Long-Evans rats and CFW mice. Females were studied for 2 consecutive cycles of pregnancy and lactation. During the first lactation, aggression was tested 2 times per week for 3 weeks in order to select animals that attacked at least once. During the second lactation, both pup care and aggressive behavior were assessed in detail. Testing occurred twice in each lactation week, with postpartum days 1–7, 8–14, and 15–21 considered weeks 1, 2, and 3, respectively. Maternal behavior towards 3 pups was observed for 5 minutes, followed by a confrontation with an intruder. Lactating females encountered female intruders once per week, and male intruders in the alternate weekly test. The same behaviors were measured in the 2 species, except for the tail rattle exhibited by mice and the aggressive posture shown by rats. Lactating rats and mice show similar decreases in pup care behavior as lactation progresses in time; yet the factors associated with peak levels of aggression differ between species. In Long-Evans rats, female intruders receive more attacks, threats, and aggressive postures than males. Frequency of attack bite and sideways threat declines in each passing week of lactation. Lactating mice are more aggressive toward male intruders throughout the lactation period. Mice still attack and threaten during the third week of lactation, but less often in comparison to the first week. Therefore, peak levels of aggression vary in mice and rats both as a function of intruder sex and lactation week.     

Relationship between maternal aggression and maternal care in the rat

Aggression among female rats is almost entirely confined to the period of late pregnancy and lactation. Behaviorally it is similar to the aggression of males including piloerection and lateral attacks, but it differs in its function. Unlike male aggression which serves to establish a social hierarchy and a territory, i. e., is competitive, maternal aggression is protective, i. e., it serves to prevent predation of the mother's offspring. In this respect it is closely related temporally and causally to maternal care; if the offspring are removed maternal aggression wanes almost immediately–its function no longer exists! Studies on aggression by mothers, among rats, from the author's laboratory are reviewed and comparisons made with maternal care. As noted, maternal aggression and maternal care are closely related during the cycle of maternal behavior and they share a similar hormonal basis and possibly the effect of uterine stimulation, but maternal care requires prolactin and the decline of progesterone while maternal aggression appears independent of pituitary hormones and does not require a decline in progesterone. Maternal aggression like maternal care appears to be organized into a hormonal phase, during pregnancy, parturition, and for about a week postpartum and a nonhormonal phase thereafter. Bilateral radiofrequency lesions of the lateral midbrain peripeduncular nucleus (PPN) produce deficits in maternal aggression if made on lactation day 7 (L7), but not earlier, without producing significant deficits in maternal behavior. Experiments showed that the PPN does not mediate hormonally stimulated maternal aggression; it appears to mediate only nonhormonally stimulated maternal aggression. Studies on the role of pregnancy hormones on long-term retention of maternal aggression and the role of olfaction in maternal aggression are also reviewed. © 1994 Wiley-Liss, Inc.     

Sensory control of maternal aggression in Rattus norvegicus

Female rats become aggressive toward adult conspecifics during lactation. This change in social affect is dependent on the presence of the offspring, because maternal aggression disappears when the pups are removed. It was found that a similar decline occurs when the litter is placed in a glass flask while remaining in the home cage. In contrast, maternal aggression persists following placement of the pups in a nylon mesh bag. The pups did not vocalize while being in the mesh bags, so it appears that olfactory cues from the offspring constitute a critical element in the maintenance of maternal aggression in the rat. It has been suggested that the odor not only of the pups but also of the intruder may contribute to eliciting aggressive behavior in lactating rodents. In line with this proposal, it was found that mother rats spend about one third of the time preceding the first attack sniffing the body of the intruder. In contrast to findings in mice, housing of the prospective intruder behind a double wire mesh partition in the lactating female's home cage failed to reduce her aggressiveness toward him. Rats, then, may require more intimate contact with an individual than do mice for the aggression-reducing effect of familiarization to be observed.     

Effects of daily and acute restraint stress during lactation on maternal aggression and behavior in mice

A decreased reactivity to stressors during lactation might heighten the expression of maternal care (including defense of offspring) by minimizing the extent to which stress can impact maternal care. Although stressors applied during pregnancy have variable effects on maternal aggression (or defense of offspring), to date no study has examined the effects of stress applied during the postpartum period on maternal aggression. In this study, we examined the effects of both daily and acute restraint stress (30 min) applied postpartum on maternal aggression and other maternal behaviors. Daily restraint (ending 2 h before testing) did not alter any measure of maternal behavior, including nursing, licking and grooming of pups and pup retrieval, or any measure of maternal aggression. In contrast, acute stress significantly impaired total time aggressive and number of attacks, but pup retrieval was normal. c-Fos levels were significantly elevated in a number of brain regions in association with acute stress, including lateral septum (LS), caudal periaqueductal gray and medial amygdala (MeA), suggesting possible sites where stress reactivity could alter aggression. Together, the results indicate that acute restraint stress impairs maternal aggression and provide a starting point for future studies examining how stress reactivity pathways may intersect with maternal aggression pathways.     

Anxiety and maternal aggression in house mice (Mus musculus): a look at interindividual variability

The hypotheses were tested that mouse motherhood is accompanied by decreased reactivity to aversive stimuli and that female anxiety is inversely related to the probability of displaying intense forms of postpartum aggression. Outbred Swiss female mice were tested for anxiety in a light/dark choice test when virgin, pregnant, or lactating, and then tested for maternal aggression (5-min exposure to a male intruder) on postpartum Day 7. Anxiety declined in pregnant and lactating females when compared with virgin animals. Furthermore, females who displayed higher scores of postpartum fighting were less anxious in the previous test regardless of reproductive stage. Part of interindividual variability in postpartum aggression might thus be related to differences in the extent to which individuals perceive and react to anxiogenic situations. In addition, the higher emotionality characterizing the C57BL/6 and DBA/2 inbred strains may be responsible for the lack of a clear-cut exhibition of maternal aggression in these two strains.     

Prenatal depression effects on early development: A review

This review of recent research on prenatal depression suggests that it is a strong predictor of postpartum depression and is more common than postpartum depression. Prenatal depression has been associated with excessive activity and growth delays in the fetus as well as prematurity, low birthweight, disorganized sleep and less responsiveness to stimulation in the neonate. Infants of depressed mothers have difficult temperament, and later in development attentional, emotional and behavioral problems have been noted during childhood and adolescence, as well as chronic illnesses in adulthood. Several variables have confounded the effects of prenatal depression including comorbid anxiety and anger as well as stressful life events. Potential mediating variables are low prenatal maternal dopamine and serotonin levels and elevated cortisol and norepinephrine. The associated intrauterine artery resistance may limit blood flow, oxygen and nutrients to the fetus. Some studies also suggest the heritability of developmental problems for the children of prenatally depressed mothers, including ADHD and antisocial behavior. Multivariate, longitudinal research is needed to disentangle these confounding and mediating variables.     

Maternal aggression: disruption by perioral anesthesia in lactating Long-Evans rats (Rattus norvegicus)

Role of perioral somatosensation in the display of maternal aggression in Long-Evans Norway rats (Rattus norvegicus) was investigated during early lactation by local anesthesia of the mystacial pads with lidocaine, which blocks conduction in the infraorbital nerve. Acute perioral anesthesia markedly reduced the likelihood that maternal aggression was expressed; this effect of perioral anesthesia was not ameliorated by a repeated test with the same treatment or by pretreatment fighting experience. The dams that fought with the intruder during perioral anesthesia did so after greatly increased sniffing contact and with decreased vigor compared with controls. Males that were attacked tended to freeze, whereas males that were not attacked were active. Thus, trigeminal afferents are critical for the initiation and normal execution of maternal aggression responses in Norway rats.     

Maternal aggression in mice: Protection of young is a by-product of attacks at the home site

Lactating female mice attacked male intruders in their home cages but showed little attack behavior either in novel cages or in cages with which they had been familiarized. Presence or absence of young did not determine the occurrence of maternal aggression, whereas attacks on the young by the intruder decreased maternal aggression and increased cannibalism of pups by the dams. Apparently, if the function of maternal aggression in mice is protection of the young, such protection occurs because the pups are in a place where attacks are likely to occur and not because the dam “defends” the young.     

Differential Effects of Short- and Long-Term Early Maternal Separation on Subsequent Maternal Behavior in Rats

Female Sprague-Dawley pups were separated from mothers every other day for 8 hr (long-term separation/LTS), 4 hr (short-term separation/STS), or 0 hr (no separation/NS) from postnatal day 2–20. In adulthood, they were mated and tested for maternal behaviors during two lactations. It was expected that females separated from mothers as pups would show deficits in maternal behavior as adults. Contrary to expectations, LTS showed better nest building and grouped young faster during both lactations. LTS were first to display aggression and displayed more aggression during the second lactation. Notably, while some measures decreased from first to second lactation in NS and STS, LTS maintained levels of maternal care. These results suggest that extended periods of maternal separation may exaggerate some aspects of maternal behavior.     

Perinatal maternal mental health and infant socio-emotional development: A growth curve analysis using the MPEWS cohort

Pregnancy and the early post partum period are widely understood as a critical period for the infant’s emotional development and the earliest influence shaping social interaction. The present study aims to understand the potential influence of both antenatal and postnatal maternal anxiety and depressive symptoms on socio-emotional outcomes in offspring aged 12 months. The study used longitudinal data from a prospective cohort study on Australian pregnant women and their children. Data were available for 282 mothers and their children. Maternal depressive and anxiety symptoms were measured in early pregnancy, trimester three of pregnancy, six and 12 months postpartum. Social and emotional development in children was measured using the Brief Infant and Toddler Social Emotional Assessment (BITSEA) at 12 months. Using growth curve analysis of 4 waves of repeated measurement to examine intercept and slope, we found that both initial maternal depression and anxiety symptom levels, and the growth of these symptoms over time, predicted more problems with children’s social and emotional development. In the final model anxiety accounted for 19% of the variance in child socio-emotional problems and depression 23% of variance. The results emphasise the importance of perinatal maternal mental health as a potential risk factor for child development. This carries important implications for policy development, such as the need to build early identification and early intervention models in to the current clinical practice for perinatal care, specifically, to develop targeted screening, assessment and interventions to address maternal mental health issues for at-risk parents during pregnancy, and continuing monitoring of young children whose mothers have experienced perinatal mental health difficulties.     

On the dual nature of maternal aggression in rats

Presentation of a natural predator, a cat, was used to differentiate elements of maternal attack by female rats on a male intruder. Following exposure (without direct physical contact) of post-partum females to a cat or to a toy stuffed cat (control group), the females were replaced in their home cages and presented with a male intruder rat. Cat exposure reliably decreased lateral attack to the intruder, as well as locomotion, but had no effect on either jump attack or an upright defensive posture (boxing). Since predator exposure produces a somewhat durable increase in defense, along with inhibition of nondefensive behavior, these results suggest that maternal aggression represents a mixture of offensive, usually related to competition, and defensive (protective) behaviors. The results indicate that maternal aggression, as a parental care behavior, appears to be at least partially resistant to fear. © 1996 Wiley-Liss, Inc.     

Effect of conspecific sex on aggression during pregnancy and lactation in golden hamsters

The effect of conspecific sex on maternal aggression in hamsters was determined by comparing the frequency of aggressive responses by dams continuously housed with either a virgin male or female cagemate during pregnancy and lactation. Dams easily established aggressive dominance over male cagemates soon after pairing, and their aggression was low thereafter for the duration of pregnancy and lactation. The aggression of dams with females, on the other hand, tended to fluctuate with highs during mid pregnancy and mid lactation and lows around birth. When dam aggression was low around birth, female cagemates frequently became aggressively dominant, and several dams lost their litters. The higher aggression of dams toward females than males is probably a reflection of greater intrasexual competition for environmental resources that includes pups.     

Mediators of aggression among young adult offspring of depressed mothers

The current article explores the connection between maternal depression and offspring aggression during the transition to adulthood, expanding the scope of prior research on this topic. Both family-level factors (including parent-child relationship quality and maternal romantic relationship quality) and youth factors (including depression history and social functioning in midadolescence) were tested as potential mediators in a longitudinal community sample of 710 youth at ages 15 and 20. The results suggest that maternal depression confers a risk for higher levels of aggressive behavior by offspring at age 20. Structural equation models suggested that the association between maternal depression and youth aggression is fully mediated by youth history of depression by midadolescence, even when accounting for the stability of aggression between ages 15 and 20. Parent-child relationship quality, youth social functioning, and maternal relationship quality were not unique mediators of this association. Limitations and implications are discussed.     

Associations Between Maternal Mental Health and Child Emotional and Behavioral Problems: Does Prenatal Mental Health Matter?

This study examined associations between elevated symptoms of prenatal depression or anxiety and offspring emotional and behavioral problems during mid to late childhood taking into account the impact of later maternal mental health symptoms. The sample consisted of 2,891 women and their children (49 % male) from a prospective, community-based study, the Avon Longitudinal Study of Parents and Children. Women completed measures of depressive (Edinburgh Postnatal Depression Scale) and anxious (Crown Crisp Experiential Index) symptoms at regular intervals beginning in pregnancy. Mothers and teachers assessed offspring emotional and behavioral problems using the Strengths and Difficulties Questionnaire when children were 10–11 years old. Multivariable regression models were fit to address study hypotheses. Exposure to elevated symptoms of maternal depression during pregnancy was associated with increased total offspring emotional and behavioral problems, even after controlling for later maternal mental health problems and a range of sociodemographic and psychosocial characteristics, according to mothers’ but not teachers’ reports. Similarly, children exposed to elevated symptoms of maternal anxiety during pregnancy were reported to have increased total emotional and behavioral problems by mothers but not by teachers. We found support for modest associations between elevated symptoms of maternal depression and anxiety during the prenatal period and certain domains of offspring emotional and behavioral problems in mid to late childhood above and beyond the impact of later maternal mental health problems. These findings highlight the need for additional clinical and research attention to the prenatal period and to both maternal depression and anxiety.     

Current and Past Maternal Depression, Maternal Interaction Behaviors, and Children’s Externalizing and Internalizing Symptoms

Relations among past maternal depressive disorder, current depressive symptoms, current maternal interaction behaviors, and children's adjustment were examined in a sample of 204 women and their young adolescent offspring (mean age = 11.86, SD = 0.55). Mothers either had (n = 157) or had not (n = 57) experienced at least one depressive disorder during the child's life. Mothers and children participated in a problem-solving task, video-taped for later coding. Mothers with current depressive symptoms and those with histories of chronic/severe depressive disorders displayed fewer positive behaviors toward their children; mothers with current depressive symptoms also showed more negative behaviors with their children. The relation between mothers' depression history and their behavior during the interaction with their child was partially mediated by mothers' current mood state. Moreover, high levels of maternal negativity and low levels of positivity during the problem-solving task were related to children's externalizing problems. Maternal positivity partially mediated the relation between maternal depression and children's externalizing symptoms. These findings highlight the importance of providing parenting interventions for depressed mothers.     

Behavioral and emotional response of Japanese macaque (Macaca fuscata) mothers after their offspring receive an aggression

The authors of this study investigated the behavioral and emotional response of female Japanese macaques (Macaca fuscata) to an aggression received by their offspring to evaluate the existence of cognitive empathic responses in a naturalistic setting. After their offspring received an aggression, mothers did not direct increased affiliative contacts to them. The factors likely to affect the degree of distress in the offspring or the perceived risk for the mother failed to appropriately modulate maternal behavior. Finally, mothers did not increase their frequency of scratching (a behavioral indicator of anxiety) after their offspring had received an aggression. The results suggest Japanese macaque mothers may be unable to understand their offspring's need for distress alleviation after the receipt of aggression.     

Maternal Psychiatric Disorders, Parenting, and Maternal Behavior in the Home During the Child Rearing Years

Data from the Children in the Community Study, a community-based longitudinal study, were used to investigate associations between maternal psychiatric disorders and child-rearing behaviors. Maternal psychiatric symptoms and behavior in the home were assessed in 782 families during the childhood and adolescence of the offspring. Maternal anxiety, depressive, disruptive, personality, and substance use disorders were independently associated with current and subsequent parenting difficulties and other problems in the home during the child rearing years, after co-occurring disorders and offspring behavior problems were controlled statistically. Maternal personality disorders were most consistently associated with problems in the home during the child rearing years. Less than 1 of 3 mothers with disorders reported having received treatment. Those who received treatment were significantly less likely to experience multiple difficulties in the home during the child rearing years. These findings suggest that maternal psychiatric disorder may be an important determinant of problematic maternal behavior in the home during the child rearing years. Improved recognition and treatment of maternal psychiatric disorders may help to reduce the amount of maladaptive parenting behavior that many youths might otherwise be likely to experience.     

The Role of Pre- and Postnatal Timing of Family Risk Factors on Child Behavior at 36 months

Children growing up in disharmonious families with anxious/depressed mothers are at risk for emotional and behavioral difficulties, however whether these associations reflect postnatal environment, prenatal exposure, or an overall liability is still unclear. This study used prospectively collected data from 24,259 participants of the Norwegian Mother and Child Cohort Study (MoBa). Mothers reported on anxiety/depression and family disharmony twice in pregnancy and twice post pregnancy, as well as on their child’s physical aggression and crying behavior at age 36 months. First, results from an autoregressive cross-lagged model showed a substantial stability in both maternal anxiety/depression and family disharmony from pregnancy to 18 months postnatal, but there was no indication that family disharmony led to maternal anxiety/depression, or the other way around. Second, structural equation models further suggests that the main risk derived from an overall liability, that is, a lasting effect of family risks that spanned the two time periods.     

Maternal perinatal mental health: Associations with bonding,mindfulness, and self-criticism at 18 months’ postpartum

The perinatal period is a time of significant transition for women, with changes in maternal mental health from pregnancy to 18 months’ postpartum. This study specifically analyzes maternal self-criticism and mindfulness during pregnancy and at 18 months’ postpartum, and their associations with bonding. A longitudinal study (30 weeks’ gestation–18 months’ postpartum) assessed 32 mother–infant dyads, examining changes in maternal depression, anxiety, self-criticism, and mindfulness. In addition, associations between maternal variables during pregnancy and bonding were investigated. Maternal depression and self-criticism significantly increased from pregnancy to postpartum. Maternal anxiety, self-criticism, and facets of mindfulness during pregnancy were also associated with mother–infant bonding at 18 months. Maternal mental health during pregnancy is subject to change postchildbirth. The lack of control and autonomy accompanying motherhood may result in an increase in self-criticism during this period. Such feelings may elevate a woman's vulnerability to postpartum depression and have consequences for later maternal bonding. Early identification of at-risk mothers is important to increase likelihood of positive outcomes.