Bibliometric analysis on cannibalism/infanticide and maternal aggression towards pups in laboratory rodents.

Animal welfare has evolved during the past decades to improve not only the quality of life of laboratory rodents but also the quality and reproducibility of scientific investigations. Bibliometric analysis has become an important tool to complete the current knowledge with academic databases. Our objective was to investigate whether scientific research on cannibalism/infanticide is connected with maternal aggression towards the offspring in laboratory rodents. To carry out our research, we performed a specific search for published articles on each concept. Results were analyzed in the open-source environment RStudio with the package Bibliometrix. We obtained 253 and 134 articles for the first search (cannibalism/infanticide) and the second search (maternal aggression towards the pups) respectively. We observed that the interest in infanticide/cannibalism started in the 1950s, while researchers started showing interest in maternal aggression towards the pups 30 years later. Our analyses indicated that maternal aggression had better citations in scientific literature. In addition, although our results showed some common features (e.g. oxytocin or medial preoptic area in the brain), we observed a gap between cannibalism/infanticide and maternal aggression towards the pups with only 14 published articles in common for both the searches. Therefore, we recommend researchers to combine both concepts in further investigations in the context of cannibalism for better dissemination and higher impact in laboratory rodents' welfare research.

Enhanced maternal behaviors in a mouse model of congenital blindness.

In mammals, mothering is one of the most important prosocial female behavior to promote survival, proper sensorimotor, and emotional development of the offspring. Different intrinsic and extrinsic factors can initiate and maintain these behaviors, such as hormonal, cerebral, and sensory changes. Infant cues also stimulate multisensory systems and orchestrate complex maternal responsiveness. To understand the maternal behavior driven by complex sensory interactions, it is necessary to comprehend the individual sensory systems by taking out other senses. An excellent model for investigating sensory regulation of maternal behavior is a murine model of congenital blindness, the ZRDBA mice, where both an anophthalmic and sighted mice are generated from the same litter. Therefore, this study aims to assess whether visual inputs are essential to driving maternal behaviors in mice. Maternal behaviors were assessed using three behavioral tests, including the pup retrieval test, the home cage maternal behavior test, and the maternal aggression test. Our results show that blind mothers (1) took less time to retrieve their offspring inside the nest, (2) spent more time nursing and licking their offspring in the second- and third-week postpartum, and (3) exhibited faster aggressive behaviors when exposed to an intruder male, compared to the sighted counterparts. This study provides evidence that congenitally blind mothers show more motivation to retrieve the pups, care, and protection towards their pups than sighted ones, likely due to a phenomenon of sensory compensation.

The Role of Oxytocin in Domestic Animal's Maternal Care: Parturition, Bonding, and Lactation.

Oxytocin (OXT) is one of the essential hormones in the birth process; however, estradiol, prolactin, cortisol, relaxin, connexin, and prostaglandin are also present. In addition to parturition, the functions in which OXT is also involved in mammals include the induction of maternal behavior, including imprinting and maternal care, social cognition, and affiliative behavior, which can affect allo-parental care. The present article aimed to analyze the role of OXT and the neurophysiologic regulation of this hormone during parturition, how it can promote or impair maternal behavior and bonding, and its importance in lactation in domestic animals.

Decoupling pioneering traits from latitudinal patterns in a north American bird experiencing a southward range shift.

Ecogeographic rules describe spatial patterns in biological trait variation and shed light on the drivers of such variation. In animals, a consensus is emerging that 'pioneering' traits may facilitate range shifts via a set of bold, aggressive and stress-resilient traits. Many of these same traits are associated with more northern latitudes, and most range shifts in the northern hemisphere indicate northward movement. As a consequence, it is unclear whether pioneering traits are simply corollaries of existing latitudinal variation, or whether they override other well-trodden latitudinal patterning as a unique ecogeographic rule of phenotypic variation. The tree swallow Tachycineta bicolor is a songbird undergoing a southward range shift in the eastern United States, in direct opposition of the poleward movement seen in most other native species' range shifts. Because this organic range shift countervails the typical direction of movement, this case study provides for unique ecological insights on organisms and their ability to thrive in our changing world. We sampled female birds across seven populations, quantifying behavioural, physiological and morphological traits. We also used GIS and field data to quantify a core set of ecological factors with strong ties to these traits as well as female performance. Females at more southern expansion sites displayed higher maternal aggression, higher baseline corticosterone and more pronounced elevation of corticosterone following a standardized stressor, contrary to otherwise largely conserved latitudinal patterning in these traits. Microhabitat variation explained some quantitative phenotypic variation, but the expansion and historic ranges did not differ in openness, distance to water or breeding density. This countervailing range shift therefore suggests that pioneering traits are not simply corollaries of existing latitudinal variation, but rather, they may override other well-trodden latitudinal patterning as a unique ecogeographic rule of phenotypic variation.

VMHvllCckar cells dynamically control female sexual behaviors over the reproductive cycle.

Sexual behavior is fundamental for the survival of mammalian species and thus supported by dedicated neural substrates. The ventrolateral part of ventromedial hypothalamus (VMHvl) is an essential locus for controlling female sexual behaviors, but recent studies revealed the molecular complexity and functional heterogeneity of VMHvl cells. Here, we identify the cholecystokinin A receptor (Cckar)-expressing cells in the lateral VMHvl (VMHvllCckar) as the key controllers of female sexual behaviors. The inactivation of VMHvllCckar cells in female mice diminishes their interest in males and sexual receptivity, whereas activating these cells has the opposite effects. Female sexual behaviors vary drastically over the reproductive cycle. In vivo recordings reveal reproductive-state-dependent changes in VMHvllCckar cell spontaneous activity and responsivity, with the highest activity occurring during estrus. These in vivo response changes coincide with robust alternation in VMHvllCckar cell excitability and synaptic inputs. Altogether, VMHvllCckar cells represent a key neural population dynamically controlling female sexual behaviors over the reproductive cycle.

Glutamatergic neurons from the medial prefrontal cortex to the dorsal raphe nucleus regulate maternal aggression in lactating mice.

Glutamatergic signals in the dorsal raphe nucleus (DRN) regulate maternal aggression and care in mice. We examined whether glutamatergic input from the medial prefrontal cortex (mPFC) to the DRN might regulate maternal aggression and care in mice. In the maternal aggression test, each dam was exposed to an identical intruder male twice for 5 min, 60 min apart. During the latter trial (opt trial), the terminals of glutamatergic neurons from the mPFC to the DRN were manipulated using optogenetic techniques. Compared to the former trial (pre-opt trial), the inhibition of glutamatergic input in the opt trial decreased bite frequency and prevented the shortening of biting latency. In contrast, the activation of glutamatergic input at 5 Hz increased the biting frequency. Meanwhile, the activation of glutamatergic input at 1, 10, and 20 Hz prevented the shortening of biting latency without affecting biting frequency. In the maternal care test, activation of glutamatergic input at 5 Hz did not affect maternal care. Our results suggest that glutamatergic neurons from the mPFC to the DRN differently regulate maternal aggression, depending on temporal patterns of their activation, and that the glutamatergic signals that enhance maternal aggression are not involved in the regulation of maternal care.

Make war not love: The neural substrate underlying a state-dependent switch in female social behavior.

Female mice exhibit opposing social behaviors toward males depending on their reproductive state: virgins display sexual receptivity (lordosis behavior), while lactating mothers attack. How a change in reproductive state produces a qualitative switch in behavioral response to the same conspecific stimulus is unknown. Using single-cell RNA-seq, we identify two distinct subtypes of estrogen receptor-1-positive neurons in the ventrolateral subdivision of the female ventromedial hypothalamus (VMHvl) and demonstrate that they causally control sexual receptivity and aggressiveness in virgins and lactating mothers, respectively. Between- and within-subject bulk-calcium recordings from each subtype reveal that aggression-specific cells acquire an increased responsiveness to social cues during the transition from virginity to maternity, while the responsiveness of the mating-specific population appears unchanged. These results demonstrate that reproductive-state-dependent changes in the relative activity of transcriptomically distinct neural subtypes can underlie categorical switches in behavior associated with physiological state changes.

Maternal behavior, novelty confrontation, and subcortical c-Fos expression during lactation period are shaped by gestational environment.

The environmental context during gestation may modulate the postpartum variations in maternal behaviors observed within different animal species. Most of our experimental knowledge on this phenomenon and its physiological effects have been gained by confronting the pregnant mother with stressful situations, with the consensual results indicating a reduced maternal behavior and a hyper reactivity of stress-related neural paths. Here, in contrast, by exposing nulliparous rats strictly during pregnancy to a standard laboratory environment (STD) or a highly stimulating sensory and social environment (EE), we investigated the hypothesis that subjects frequently exposed to social stimuli and novel situations during pregnancy will show postpartum changes in subcortical brain areas' activity related to the processing of social stimuli and novelty, such that there will be modifications in maternal behavior. We found that EE mothers doubled the levels of licking and grooming, and active hovering over pups during the first postpartum week than STD dams, without a difference in the time of contact with the pups. Associated with these behaviors, EE dams showed increased c-Fos immunoreaction in hypothalamic nuclei and distinct responses in amygdalar nuclei, than STD dams. In the maternal defensive test, EE dams tripled the levels of aggressive behaviors of the STD rats. Additionally, in two different tests, EE mothers showed lower levels of postpartum anxiety-like behaviors when confronted with novel situations. Our results demonstrate that the activity of brain areas related to social behavior is adaptable by environmental circumstances experienced during gestation, presumably to prepare the progeny for these particular conditions.

Opioid use during pregnancy can impair maternal behavior and the Maternal Brain Network: A literature review.

Opioid Use Disorder (OUD) is a global epidemic also affecting women of reproductive age. A standard form of pharmacological treatment for OUD is Opioid Maintenance Therapy (OMT) and buprenorphine has emerged as the preferred treatment for pregnant women with OUD relative to methadone. However, the consequences of BUP exposure on the developing Maternal Brain Network and mother-infant dyad are not well understood. The maternal-infant bond is dependent on the Maternal Brain Network, which is responsible for the dynamic transition from a "nulliparous brain" to a "maternal brain". The Maternal Brain Network consists of regions implicated in maternal care (e.g., medial preoptic area, nucleus accumbens, ventral pallidum, ventral tegmentum area) and maternal defense (e.g., periaqueductal gray). The endogenous opioid system modulates many of the neurochemical changes in these areas during the transition to motherhood. Thus, it is not surprising that exogenous opioid exposure during pregnancy can be disruptive to the Maternal Brain Network. Though less drastic than misused opioids, OMTs may not be without risk of disrupting the neural and molecular structures of the Maternal Brain Network. This review describes the Maternal Brain Network as a framework for understanding how pharmacological differences in exogenous opioid exposure can disrupt the onset and maintenance of the maternal brain and summarizes opioid and OMT (in particular buprenorphine) use in the context of pregnancy and maternal behavior. This review also highlights future directions for evaluating exogenous opioid effects on the Maternal Brain Network in the hopes of raising awareness for the impact of the opioid crisis not only on exposed infants, but also on mothers and subsequent mother-infant bonds.

Investigation of the factors that induce maternal aggression towards juveniles among several mouse strains.

Maternal care and aggression are representative of maternal behavior among lactating female mice. Even neonates and juveniles, who are not biological offspring, can induce maternal care and aggression in dams. Here, we investigated the factors that induce maternal aggression through exposure to juvenile mice. We first addressed the role of intruder age on the induction of maternal aggression in dams. BALB/c dams displayed attacking behavior towards 14-day-old C57BL/6J male intruders. Consumption of food pellets during the weaning period was unlikely to affect the induction of attacking behavior, as the intruders reared by breastfeeding, without food pellets, induced intensive attacking behavior in dams. Next, we compared the intruder-mediated induction of attacking behavior through different mouse strains. Specifically, BALB/c intruders induced a lower level of attacking behavior in BALB/c or ICR dams, compared to the other strains tested. However, BALB/c intruders induced intense attacking behavior in C57BL/6N dams, indicating that the occurrence of attacking behavior is dependent on the strains of dams as well as intruders. A cross-fostering experiment highlighted that the rearing by an original mother was required for C57BL/6J juveniles to induce attacking behavior. In contrast, BALB/c intruders may emit an inhibitory factor that limits attacking behavior. We finally explored which parts of the body emit these aggression-inducible signals. Removal of body hair around the proximal tail of the intruders significantly decreased the attacking behavior of dams, demonstrating that chemical cues, namely pheromones, attached to the body hair around the proximal tail may be essential for inducing attacking behavior in dams.

Trajectories of maternal aggression in early childhood: Associations with parenting stress, family resources, and neighborhood cohesion.

BACKGROUND: The effects of family risk on parenting can be ameliorated or exacerbated depending on factors internal (e.g., appraisals, regulation) and external (e.g., resources, social support) to the role of parenting. Therefore, it is important to distinguish between sources of stress when exploring associations with parenting behaviors. OBJECTIVE: We aimed to identify trajectories of maternal aggression among families across various levels of risk, and explore associations with factors internal and external to parenting. PARTICIPANTS AND SETTING: Participants included children in large U.S. cities born between 1998 and 2000, followed through age 9, in the Fragile Families and Child Well-being Study with medical records data available (N = 3529). METHOD: Latent growth curve modeling was conducted to identify trajectories of maternal aggression measured through a survey at child age 3, 5, and 9. Correlates of maternal aggression (i.e., family risk for maltreatment, income-to-poverty ratios, maternal education, parenting stress, and neighborhood cohesion) were measured through medical records and maternal surveys at birth, age 1, and age 3. RESULTS: Maternal aggression similarly declined between child age 3 and 9 across low-, moderate-, and high-risk families. Across all families, neighborhood social cohesion was significantly, negatively associated with maternal aggression, (ß's = -.20 to -.28, p's < .001) and increases in parenting stress were significant predictors among Low Risk (ß = .12, p = .006) and High Risk (ß = .10, p = .02) families. CONCLUSION: The results suggest that families could benefit from supportive neighborhood environments or parenting stress reduction techniques, regardless of level of risk at birth.

The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents.

The appropriate display of social behaviors is essential for the well-being, reproductive success and survival of an individual. Deficits in social behavior are associated with impaired N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. In this review, we describe recent studies using genetically modified mice and pharmacological approaches which link the impaired functioning of the NMDA receptors, especially of the receptor subunits GluN1, GluN2A and GluN2B, to abnormal social behavior. This abnormal social behavior is expressed as impaired social interaction and communication, deficits in social memory, deficits in sexual and maternal behavior, as well as abnormal or heightened aggression. We also describe the positive effects of pharmacological stimulation of the NMDA receptors on these social deficits. Indeed, pharmacological stimulation of the glycine-binding site either by direct stimulation or by elevating the synaptic glycine levels represents a promising strategy for the normalization of genetically-induced, pharmacologically-induced or innate deficits in social behavior. We emphasize on the importance of future studies investigating the role of subunit-selective NMDA receptor ligands on different types of social behavior to provide a better understanding of the underlying mechanisms, which might support the development of selective tools for the optimized treatment of disorders associated with social deficits.

More than reproduction: Central gonadotropin-releasing hormone antagonism decreases maternal aggression in lactating rats.

Gonadotropin-releasing hormone (GnRH) is a major regulator and activator of the hypothalamic-pituitary-gonadal axis. Many studies have demonstrated the importance of GnRH in reproduction and sexual behaviour. However, to date, only a single study shows an involvement of GnRH in maternal behaviour where a 30% reduction of GnRH neurones abolishes a mother's motivation to retrieve pups. On this basis, we aimed to investigate the effects of acute central GnRH receptor blockade in lactating rats on maternal care under non-stress and stress conditions, maternal motivation in the pup retrieval test, maternal anxiety on the elevated plus maze, and maternal aggression in the maternal defence test. We found that acute central infusion of a GnRH antagonist ([d-Phe2,6 ,Pro3 ]-luteinising hormone-releasing hormone; 0.5 ng 5 µL-1 ) impaired a mother's attack behaviour against a female intruder rat during the maternal defence test compared to vehicle controls. However, in contrast to the previous study on reduced GnRH neurones, acute central GnRH antagonism did not affect pup retrieval, nor any other parameter of maternal behaviour or maternal anxiety. Taken together, GnRH receptor activation is mandatory for protection of the offspring. These findings shed new light on GnRH as a neuropeptide acting not exclusively on the reproductive axis but, additionally, on maternal behaviour including pup retrieval and maternal aggression.

Serotonin and motherhood: From molecules to mood.

Emerging research points to a valuable role of the monoamine neurotransmitter, serotonin, in the display of maternal behaviors and reproduction-associated plasticity in the maternal brain. Serotonin is also implicated in the pathophysiology of numerous affective disorders and likely plays an important role in the pathophysiology of maternal mental illness. Therefore, the main goals of this review are to detail: (1) how the serotonin system of the female brain changes across pregnancy and postpartum; (2) the role of the central serotonergic system in maternal caregiving and maternal aggression; and (3) how the serotonin system and selective serotonin reuptake inhibitor medications (SSRIs) are involved in the treatment of maternal mental illness. Although there is much work to be done, studying the central serotonin system's multifaceted role in the maternal brain is vital to our understanding of the processes governing matrescence and the maintenance of motherhood.

Mom doesn't care: When increased brain CRF system activity leads to maternal neglect in rodents.

Mothers are the primary caregivers in mammals, ensuring their offspring's survival. This strongly depends on the adequate expression of maternal behavior, which is the result of a concerted action of "pro-maternal" versus "anti-maternal" neuromodulators such as the oxytocin and corticotropin-releasing factor (CRF) systems, respectively. When essential peripartum adaptations fail, the CRF system has negative physiological, emotional and behavioral consequences for both mother and offspring often resulting in maternal neglect. Here, we provide an elaborate and unprecedented review on the implications of the CRF system in the maternal brain. Studies in rodents have advanced our understanding of the specific roles of brain regions such as the limbic bed nucleus of the stria terminalis, medial preoptic area and lateral septum even in a CRF receptor subtype-specific manner. Furthermore, we discuss potential interactions of the CRF system with other neurotransmitters like oxytocin and noradrenaline, and present valuable translational aspects of the recent research.

Brain vasopressin signaling modulates aspects of maternal behavior in lactating rats.

The brain vasopressin system mediates various social behaviors as has been studied mostly in males. Only recently, advances in social neuroscience revealed that central vasopressin signaling via its V1a and V1b receptors also facilitates female social behavior, including maternal behavior. In this review, we show how maternal care, maternal motivation and maternal aggression of lactating rat mothers are modulated in a V1 receptor subtype- and brain region-specific manner. Measuring local release pattern of vasopressin via intracerebral microdialysis in the behaving rat mother as well as using pharmacological approaches to activate or block vasopressin receptors with subsequent behavioral observation provide detailed insight into the functional role of the vasopressin system in maternal behavior. In this context, the complementary rat animal model of high (HAB) and low anxiety-related behavior (LAB) is particularly helpful due to the genetically determined high activity of the vasopressin gene in HAB rats, which also underlies their high levels of maternal behavior. Furthermore, first studies in humans indicate that the vasopressin system in general and the V1a receptor in more particular might mediate mothering.

Social Defeat Stress, Sex, and Addiction-Like Behaviors.

Social confrontation is a form of social interaction in animals where two conspecific individuals confront each other in dispute over territory, during the formation of hierarchies, and during breeding seasons. Typically, a social confrontation involves a prevailing individual and a yielding individual. The prevailing individual often exhibits aggressive postures and launches attacks, whereas the yielding individual often adopts postures of defeat. The yielding or defeated animals experience a phenomenon known as social defeat stress, in which they show exaggerated stress as well as autonomic and endocrine responses that cause impairment of both the brain and body. In laboratory settings, one can reliably generate social defeat stress by allowing a naïve (or already defeated) animal to intrude into a home cage in which its resident has already established a territory or is nursing. This resident-intruder paradigm has been widely used in both males and females to study mechanisms in the brain that underlie the stress responses. Stress has profound effects on drug reward for cocaine, methamphetamine, alcohol, and opioids. Particularly, previous experiences with social defeat can exaggerate subsequent addiction-like behaviors. The extent of these addiction-like behaviors depends on the intensity, duration, frequency, and intermittency of the confrontation episodes. This chapter describes four types of social defeat stress: acute, repeated, intermittent, and chronic. Specifically, it focuses on social defeat stress models used in laboratories to study individual, sex, and animal strain differences in addiction-like behaviors.

Amygdala Resting Connectivity Mediates Association Between Maternal Aggression and Adolescent Major Depression: A 7-Year Longitudinal Study.

OBJECTIVE: The parent-adolescent relationship is an important predictor of adolescent mental health, especially depressive disorders. This relationship is constructed in the context of maturing emotion neurobiology and could help shape such neurobiology in ways that are important for current and future mental health. Amygdala resting-state functional networks have been linked to depression, but whether such resting connectivity is associated with parent affective behaviors or acts as a salient mediator between parenting and risk for depressive disorder is unknown. METHOD: In the present study of 128 individuals, a 7-year longitudinal design was used to examine how observed maternal aggressive behavior during mother-adolescent interactions in early adolescence (12 years) predicted amygdala (whole and subregion)-based resting connectivity in mid adolescence (16 years). In 101 of those participants, whether altered amygdala resting-state connectivity mediated the association between maternal aggressive behavior and the first onset of major depressive disorder (MDD) in late adolescence (19 years) was analyzed. RESULTS: Maternal aggression was related to resting-state functional connectivity between the amygdala and right superior temporal-posterior insula-Heschl gyri, bilateral visual cortex, and left temporal and insula cortices (the latter being driven by the centromedial amygdala subregion; p < .001). Further, amygdala and centromedial amygdala connectivity with the temporal and insula cortices mediated the association between maternal aggression and late adolescent-onset MDD (CI 0.20 to 2.87; CI 0.13 to 2.40, respectively). CONCLUSION: These findings are consistent with previous literature documenting the importance of amygdala resting networks for adolescent depression but further suggest the importance of parental affective (particularly aggressive) behavior in the development of such functional connectivity patterns during this period of peak onset for mental health disorders.

Chronic social instability in adult female rats alters social behavior, maternal aggression and offspring development.

We investigated the consequences of chronic social instability (CSI) during adulthood on social and maternal behavior in females and social behavior of their offspring in a rat model. CSI consisted of changing the social partners of adult females every 2-3 days for 28 days, 2 weeks prior to mating. Females exposed to CSI behaved less aggressively and more pro-socially towards unfamiliar female intruders. Maternal care was not affected by CSI in a standard testing environment, but maternal behavior of CSI females was less disrupted by a male intruder. CSI females were quicker to attack prey and did not differ from control females in their saccharin consumption indicating, respectively, no stress-induced sensory-motor or reward system impairments. Offspring of CSI females exhibited slower growth and expressed more anxiety in social encounters. This study demonstrates continued adult vulnerability to social challenges with an impact specific to social situations for mothers and offspring.

Tuning the brain for motherhood: prolactin-like central signalling in virgin, pregnant, and lactating female mice.

Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.