Maternal Aggression Research Articles

Further evidence for the role of nitric oxide in maternal aggression: effects of L-NAME on maternal aggression towards female intruders in Wistar rats

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.

Activation of corticotropin-releasing factor receptor 2 in lateral septum negatively regulates maternal defense.

Maternal defense (also known as maternal aggression) is impaired by corticotropin-releasing factor-(CRF) related peptides, but where these peptides inhibit defense is unknown. Lateral septum (LS) gates reactivity to stressors, contains receptors to CRF-related peptides, and during lactation shows a decreased response to CRF, suggesting LS is a key site for regulating maternal aggression. In this study, the authors examined the effects of CRF-related peptides in LS on maternal defense. LS injections of CRF (0.2 microg), urocortin (Ucn) 1 (0.2 microg), and Ucn 3 (0.25 microg) all significantly impaired maternal defense behavior. However, LS injections of CRF receptor 2 antagonist astressin-2B, but not a CRF receptor 1 antagonist, reversed the inhibitory effects of both septal CRF and Ucn 3. After intra-LS injection of peptides, c-Fos immunoreactivity was increased in ventromedial hypothalamus, lateral hypothalamus, and parabrachial nucleus, identifying these brain regions as possible downstream mediators of altered LS activity. Together, these findings indicate that CRF-related peptides similarly modulate maternal defense via CRF receptor 2, and that LS is a critical site for the negative regulation of maternal defense behavior.

Paternal influence on female behavior: The role of Peg3 in exploration, olfaction, and neuroendocrine regulation of maternal behavior of female mice.

Genomic imprinting represents a mechanism through which parent-of-origin effects on offspring development may be mediated. However, investigation of the influence of imprinted genes on behavior has been limited. Here the authors investigate the role of the maternally imprinted/paternally expressed gene, Peg3, in several aspects of behavior using both 129Sv- and B6-Peg3 mutant female mice. Virgin Peg3 females on both genetic backgrounds were less exploratory and had higher rates of defecation with strain-dependent effects on activity levels and olfactory discrimination. Reproductive success, pup retrieval, and postnatal maternal care of pups were reduced in these females whereas indices of maternal aggression were higher among B6 Peg3-KO females. Differences in maternal care were apparent in females caring for biological or cross-fostered offspring and deficits in pup retrieval apparent beyond the immediate postpartum period. Oxytocin receptor binding in the MPOA and LS was reduced in Peg3-KO females. Thus, the authors demonstrate that disruptions to Peg3 influences aspects of female behavior that are critical for mediating maternal effects on offspring development, such as postpartum licking/grooming, and that effects of Peg3 are dependent on the maternal genetic background.

Supplemental Material for GABAA Receptor Signaling in the Lateral Septum Regulates Maternal Aggression in Mice

Supplemental Material for GABAA Receptor Signaling in the Lateral Septum Regulates Maternal Aggression in Mice

Neurotensin inversely modulates maternal aggression

Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT's role in maternal defense. Intracerebroventricular (i.c.v.) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 μg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 μg) relative to vehicle, suggesting specificity of NT action on defense. Further, i.c.v. injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 μg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 μg NT or vehicle. Thirteen of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior.

Interaction of Parenting Experiences and Brain Structure in the Prediction of Depressive Symptoms in Adolescents

Although some evidence suggests that neuroanatomic abnormalities may confer risk for major depressive disorder, findings are inconsistent. One potential explanation for this is the moderating role of environmental context, with individuals differing in their biological sensitivity to context. To examine the influence of adverse parenting as an environmental moderator of the association between brain structure and depressive symptoms. Cross-sectional measurement of brain structure, adverse parenting, and depressive symptoms in early adolescents. General community. A total of 106 students aged 11 to 13 years (55 males [51%]), recruited from primary schools in Melbourne, Australia, and their mothers. Selection was based on affective temperament, aimed at producing a sample representing a broad range of risk for major depressive disorder. No participant evidenced current or past case-level depressive, substance use, or eating disorder. (1) Volumetric measures of adolescents' amygdala, hippocampus, and anterior cingulate cortex (ACC); (2) frequency of observed maternal aggressive behavior during a mother-adolescent conflict-resolution interaction; and (3) adolescent depressive symptoms. Boys with smaller right amygdalas reported more depressive symptoms. However, neither hippocampal volume nor asymmetry measures of limbic or paralimbic ACC were directly related to level of depressive symptoms. Importantly, frequency of maternal aggressive behaviors moderated the associations between both the amygdala and ACC, and adolescent symptoms. Particularly, in conditions of low levels of maternal aggressiveness, boys with larger right amygdalas, girls with smaller bilateral amygdalas, and both boys and girls with smaller left paralimbic ACC reported fewer symptoms. These findings help elucidate the complex relationships between brain structure, environmental factors, and depressive symptoms. Further longitudinal research is required to examine how these factors contribute to the onset of case-level disorder, but given that family context risk factors are modifiable, our findings do suggest the potential utility of targeted early parenting interventions.

Cerebral abscess in term newborn with perinatal asphyxia: The importance of cerebral ultrasound monitoring

Potentiating social, cognitive, and sensorimotor stimulations the Environmental Enrichment (EE) increases levels of novelty and complexity experienced by individuals. Growing evidence demonstrates that parental EE experience, even occurring in the pre-reproductive phase, affects behavioral and neural developmental trajectories of the offspring.To discover how the accumulation of early maternal complex experiences may inform and shape the social behavior of the following generation, we examined the effects of pre-reproductive enrichment of dams (post-natal days 21–72) on the play performances of their male and female adolescent offspring. Furthermore, we examined the effects of pre-reproductive enrichment on maternal behavior (during post-partum days 1–10) and male intruder aggression (on post-partum day 11). Since oxytocin modulates maternal care, social bonding, and agonistic behavior, the number of oxytocinergic neurons of the paraventricular (PVN) and supraoptic (SON) nuclei was examined in both dams and offspring.Results revealed that enriched females exhibited higher levels of pup-oriented behaviors, especially Crouching, and initiated pup-retrieval more quickly than standard females after the maternal aggression test. Such behavioral peculiarities were accompanied by increased levels of oxytocinergic neurons in PVN and SON. Moreover, pre-reproductive maternal EE cross-generationally influenced the offspring according to sex. Indeed, male pups born to enriched females exhibited a reduced play fighting associated with a higher number of oxytocinergic neurons in SON in comparison to male pups born to standard-housed females.In conclusion, pre-reproductive EE to the mothers affects their maternal care and has a cross-generational impact on the social behavior of their offspring that do not directly experiences EE.This article is part of the Special Issue entitled “Neurobiology of Environmental Enrichment”.

Deletion of corticotropin-releasing factor binding protein selectively impairs maternal, but not intermale aggression

Corticotropin-releasing factor (CRF) binding protein (CRF-BP) is a secreted protein that acts to bind and limit the activity of the neuropeptides, CRF and urocortin (Ucn) 1. We previously selected for high maternal defense (protection of offspring) in mice and found CRF-BP to be elevated in the CNS of selected mice. We also previously determined that both CRF and Ucn 1 are potent inhibitors of offspring protection when administered centrally. Thus, elevated CRF-BP could promote defense by limiting endogenous actions of CRF or Ucn 1. To test this hypothesis, we crossed the deletion for CRF-BP into the mice selected for high maternal defense and evaluated offspring protection and other maternal behaviors. CRF-BP knockout (KO) mice exhibited significant deficits in maternal aggression relative to wild-type (WT) mice in three different measures. Other maternal features were almost identical between groups, including dam and pup weight, litter size, nursing time, and pup retrieval. Both groups performed similarly in a forced swim stress test and aggression in both groups was reduced following the swim test. Virgin KO female mice exhibited higher levels of anxiety-like behavior in terms of decreased time in the light portion of the light/dark box test. For males, no differences in light/dark box or swim test were found. However, increased anxiety-like behavior in male KO mice was identified in terms of contact and approach to a novel object both with and without previous exposure to the swim test. No differences in isolation induced resident intruder male aggression were found between groups. Together, these results indicate that loss of CRF-BP selectively impairs maternal, but not intermale aggression and that loss of the gene induces anxiety-like behavior in males and females, but there are sex differences in terms of how that anxiety is revealed.

Circulating prolactin, MPOA prolactin receptor expression and maternal aggression in lactating rats

Maternal aggression is most intense in lactating rats from the 3rd to the 12th day postpartum. The purpose of this study was to determine if plasma prolactin (PRL) and prolactin receptor (PRL-R L) mRNA expression in the medial preoptic area (MPOA) of lactating rats are altered in association with maternal aggression. Lactating Sprague Dawley rats were divided into five groups and exposed for 10 min to an intruder male or to an object on postpartum day 8. Trunk blood and the brain of the dams were collected 30 or 240 min after exposure and from a non-exposed group. Lower levels of prolactin were found 30 min after the aggression test. No change was detected in the number of cells expressing PRL-R L mRNA by in situ hybridization histochemistry (ISHH) as a function of testing. However, the correlation between plasma PRL and PRL-R L mRNA expression in the mothers changed from positive in control females to negative in intruder exposed animals. These data support the concept that a maternal aggressive experience, while acutely altering PRL secretion, fails to affect PRL-R L mRNA expression.

Neonatal exposure to chlorpyrifos affects maternal responses and maternal aggression of female mice in adulthood

CD-1 mice were exposed to the organophosphate pesticide chlorpyrifos (CPF) throughout postnatal days (PND) 11–14 at the subtoxic dose of 3 mg/kg. At adolescent age, females and males underwent a sociability test in which level of sociability and social preference were measured. At adulthood only females' behavior was analyzed. Maternal behavior of CPF-exposed females was assessed on postpartum day 1 after removal of the pups for 1 h, while anxiety levels were measured in a 5 min dark–light test on postpartum day 2. Nest defense response to an unfamiliar male intruder was assessed on postpartum day 7. In addition, from birth to postpartum day 7 a detailed analysis of nest building activity was carried out. Neonatal CPF exposure does not interfere with social behavior and social preferences at adolescence, whereas at adulthood it induces significant behavioral alterations in lactating females. Motivation to build and defend the nest was decreased in CPF females that were also less anxious than controls in the dark–light paradigm. These results confirm that developmental exposure to CPF induces long-lasting alterations in selected sexual-dimorphic responses of the adult social repertoire, and suggest that early exposure to CPF might interfere with hypothalamic neuroendocrine mechanisms regulating social responses.

Central actions of arginine vasopressin and a V1a receptor antagonist on maternal aggression, maternal behavior, and grooming in lactating rats

Maternal aggression is a robust type of aggression displayed by lactating female rats. Although arginine vasopressin (AVP) has been implicated in the control of male aggression, its involvement in maternal aggression has not been thoroughly investigated. Previous neuroanatomical studies suggest that AVP may mediate the display of aggression during lactation. In the current study, AVP and an AVP V1a receptor antagonist were centrally administered to primiparous rats on days 5 and 15 of lactation, and aggression, maternal behavior, and grooming were recorded. Although AVP did not affect the number of attacks or duration of aggression, it increased the latency to initiate aggression on day 5, in addition to decreasing maternal behavior and increasing grooming. Conversely, V1a antagonist treatment increased maternal aggression on both days of lactation, decreased maternal behavior on day 15, and decreased grooming on day 5. Thus, it appears that central AVP activity modulates maternal aggression, as well as maternal behavior and grooming behavior during lactation.

Brain Oxytocin: A Key Regulator of Emotional and Social Behaviours in Both Females and Males

In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.

Symptom Patterns among Youth Exposed to Intimate Partner Violence

Children and adolescents exposed to intimate partner violence display a broad range of symptoms. We sought to differentiate symptom patterns and predictors of these patterns using a person-oriented approach. Previous cluster analysis research of exposed youth was extended to include youth PTSD symptoms and trauma history. Participants were 74 mothers who had received a police call for domestic violence, and who had a child between 2 and 17 years old. Cluster analysis was used to identify four symptom patterns among exposed youth: Typical, Asymptomatic, General Distress, and Acute PTSD. These patterns were replicated in separate cluster analyses with younger and older participants. Symptom patterns were differentiated by maternal distress, maternal aggression, and youth trauma history, but not by male partner aggression. Implications for assessment and treatment of youth exposed to intimate partner violence, and suggestions for further research, are discussed.

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.

Reciprocal influences between maternal discipline techniques and aggression in children and adolescents

Most studies assessing the link between parental discipline and child aggression have focused primarily on discipline as a cause and aggression as an outcome. In addition to the pathway from discipline to aggression, however, aggressive behavior on the part of the child may lead to future use of discipline by the parent. In this study, structural equation modeling was used to assess reciprocal influences over time between a mothers' use of discipline and aggression in children. Data were drawn from the Springfield Child Development Project, a longitudinal study of middle childhood and adolescence, focusing on antecedents of aggression. The original sample consisted of 440 mother-child dyads living in the city of Springfield, MA. Children in the sample were between 7 and 14 years of age at the first data collection period and between 12 and 19 years of age at the final data collection period. Four hypotheses were tested: (1) a mother's use of aggressive discipline predicts an increase in later child aggression, (2) child aggression predicts an increase in later use of aggressive discipline, (3) the use of reasoning predicts a decrease in later child aggression, and (4) child aggression predicts an increase in later use of reasoning. All hypotheses except number 3 were supported to some degree. Results suggest that children's early aggressive behavior leads to an increase in their mothers' use of both reasoning and aggressive discipline; in turn, increased use of aggressive discipline leads to an increase in aggression during both childhood and adolescence.

Paternal aggression in a biparental mouse: Parallels with maternal aggression

Environmental and social factors have important effects on aggressive behaviors. We examined the effect of reproductive experience on aggression in a biparental species of mouse, Peromyscus californicus. Estrogens are important in mediating aggressive behavior so we also examined estrogen receptor expression and c- fos for insights into possible mechanisms of regulation. Parental males were significantly more aggressive than virgin males, but no significant differences in estrogen receptor alpha or beta expression were detected. Patterns of c- fos following aggression tests suggested possible parallels with maternal aggression. Parental males had more c- fos positive cells in the medial amygdala, and medial preoptic area relative to virgin males. The medial preoptic area is generally considered to be relatively less important for male-male aggression in rodents, but is known to have increased activity in the context of maternal aggression. We also demonstrated through habituation–dishabituation tests that parental males show exaggerated investigation responses to chemical cues from a male intruder, suggesting that heightened sensory responses may contribute to increased parental aggression. These data suggest that, in biparental species, reproductive experience leads to the onset of paternal aggression that may be analogous to maternal aggression.

A link between mothers' disciplinary strategies and children's relational aggression

This study examines the association between maternal disciplinary strategies and children's level of relational aggression, and then compares these associations with those found with overt aggression. Eighty‐two 4th graders (aged 9–11 years) completed peer nomination measures of relational and overt aggression, and their mothers completed a questionnaire designed to assess their use of disciplinary strategies (e.g. authoritarian, authoritative, permissive). Consistent with prior research, parental reliance on authoritarian strategies was positively associated with children's level of overt aggression, especially among boys. There was also a trend towards a positive association between authoritarianism and relational aggression among both boys and girls. In addition, this study is the first to show a positive association between maternal permissiveness and relational aggression. This association appears to be specific to relational, and not overt aggression, and emerge more strongly for girls than boys. The implications of these results for understanding the developmental underpinnings of relational aggression are discussed.

A functional circuit underlying male sexual behaviour in the female mouse brain

In mice, pheromone detection is mediated by the vomeronasal organ and the main olfactory epithelium. Male mice that are deficient for Trpc2, an ion channel specifically expressed in VNO neurons and essential for VNO sensory transduction, are impaired in sex discrimination and male-male aggression. We report here that Trpc2-/- female mice show a reduction in female-specific behaviour, including maternal aggression and lactating behaviour. Strikingly, mutant females display unique characteristics of male sexual and courtship behaviours such as mounting, pelvic thrust, solicitation, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations towards male and female conspecific mice. The same behavioural phenotype is observed after VNO surgical removal in adult animals, and is not accompanied by disruption of the oestrous cycle and sex hormone levels. These findings suggest that VNO-mediated pheromone inputs act in wild-type females to repress male behaviour and activate female behaviours. Moreover, they imply that functional neuronal circuits underlying male-specific behaviours exist in the normal female mouse brain.

Parent–offspring and sibling conflict in Galápagos fur seals and sea lions

Parent–offspring conflict theory is well supported by theoretical arguments. However, empirical observations are often difficult to interpret and have contradicted one of its most appealing predictions that parent and offspring should disagree over killing of nest or littermates. We present the first examples of deadly conflict between siblings of different cohorts. In Galapagos fur seals (Arctocephalus galapagoensis) and sea lions (Zalophus wollebaeki), mothers often wean their single offspring at 2 years. This leads to a situation where up to 23% of all pups are born while the older sibling is still being nursed. Younger siblings are disadvantaged by being born lighter than neonates without older still dependent siblings. Pups born while an older sib is still dependent grow less in early life (fur seal) and suffer increased early mortality (both species) through direct aggression or scramble competition with the older sibling. This effect is much stronger in years of high sea surface temperature (El Nino) indicating low marine productivity and if the older offspring is a male. In both species, mothers interfere aggressively in this conflict by defending the younger offspring. In years of El Nino, intense resistance to maternal aggression by the older offspring happens frequently in the fur seal. Such resistance against weaning can induce maternal neglect of the newborn. Given substantial year to year variation in offspring growth, maternal aggression forces weaning in the older sibling only if it has reached sufficient size to support itself by foraging. In Galapagos fur seals, pups with older siblings can either represent insurance against loss of older offspring or extra reproductive value.

Porcine maternal infanticide as a model for puerperal psychosis

Childbirth is a period of substantial rapid biological and psychological change and a wide range of psychotic disorders can occur ranging from mild 'baby blues' to severe episodes of psychotic illnesses. Puerperal psychosis is the most extreme form of postnatal psychosis, occurring in 1 in 1,000 births. In this study, we have used the pig as an animal model for human postnatal psychiatric illness. Our aim was to identify quantitative trait loci (QTL) associated with maternal (infanticide) sow aggression. This is defined by sows attacking and killing their own newborn offspring, within 24 hr of birth. An affected sib pair whole genome linkage analysis was carried out with 80 microsatellite markers covering the 18 porcine autosomes and the X chromosome, with the aim of identifying chromosomal regions responsible for this abnormal behavior. Analysis was carried out using the non-parametric linkage test of Whittemore and Halpern, as implemented in the Merlin software. The results identified 4 QTL mapping on Sus scrofa chromosomes 2 (SSC2), 10 (SSC10), and X (SSCX). The peak regions of these QTL are syntenic to HSA 5q14.3-15, 1q32, Xpter-Xp2.1, and Xq2.4-Xqter, respectively. Several potential candidate genes lie in these regions in addition to relevant abnormal behavioral QTL, found in humans and rodents.