Role of tactile stimulation during the preweaning period on the development of the peripheral sensory sural (SU) nerve in adult artificially reared female rat.

Maternal deprivation, as a result of the artificial rearing (AR) paradigm, disturbs electrophysiological and histological characteristics of the peripheral sensory sural (SU) nerve of infant and adult male rats. Such changes are prevented by providing tactile or social stimulation during isolation. AR also affects the female rat's brain and behavior; however, it is unknown whether this early adverse experience also alters their SU nerve development or if tactile stimulation might prevent these possible developmental effects. To assess these possibilities, the electrophysiological and histological characteristics of the SU nerve from adult diestrus AR female rats that: (i) received no tactile stimulation (AR group), (ii) received tactile stimulation in the anogenital and body area (AR-Tactile group), or (iii) were mother reared (MR group) were determined. We found that the amplitude, but not the area, of the evoked compound action potential response in SU nerves of AR rats was lower than those of SU nerves of MR female rats. Tactile stimulation prevented these effects. Additionally, we found a reduction in the outer diameter and myelin thickness of axons, as well as a large proportion of axons with low myelin thickness in nerves of AR rats compared to the nerves of the MR and AR-Tactile groups of rats; however, tactile stimulation only partially prevented these effects. Our data indicate that maternal deprivation disturbs the development of sensory SU nerves in female rats, whereas tactile stimulation partially prevents the changes generated by AR. Considering that our previous studies have shown more severe effects of AR on male SU nerve development, we suggest that sex-associated factors may be involved in these processes.

Tactile stimulation prevents disruptions in male rat copulatory behavior induced by artificial rearing.

Early life social interactions in gregarious mammals provide an important source of stimulation required for the development of species-typical behaviors. In the present study, complete deprivation of maternal and littermate contact through artificial rearing was used to examine the role of early social stimulation on copulatory behavior and the ejaculate in adult rats. We found that artificially reared naïve male rats were sexually motivated; nevertheless, they did not acquire the level of sexual experience that typically occurs during copulatory training. Disrupted expression of sexual experience of artificially reared rats was demonstrated by an inconsistent pattern of ejaculatory behavior across training tests. Artificial tactile stimulation applied during isolation prevented this disruption and rats achieved ejaculation in most copulatory tests. Despite the irregularity of ejaculatory behavior in isolated rats, their sperm count and seminal plug were similar to control maternally reared (sexually experienced) and artificially-reared rats that received tactile stimulation. These results suggest that tactile sensory information provided by the mother and/or littermates to the offspring is crucial for the development of copulatory behavior. The absence of social and/or tactile stimulation during early life compromises the ability of male rats to gain sexual experience in adulthood.

Mother and sibling interactions during the preweaning period influence myelination and impulse propagation of the sensory sural nerve in the adult rat.

To investigate whether mother and sibling interactions during the preweaning period influence the histological and electrophysiological characteristics of the sensory sural nerve (SUn) in the adult rat, litters composed of 1, 3, 6, 9, and 12 male pups (P) were formed and the pups routinely weighed until postnatal day 60 (PND60). At PND9, 3P and 6P litters showed greater body weight than pups without siblings or from 9P or 12P litters, and such differences in weight were maintained until adulthood. Analysis of maternal licking at PND8 and 9 showed that pups from large litters received fewer licks than pups from small size litters. At PND60, SUn of rats from 6P and 9P litters had greater compound action potential (CAP) amplitude and a higher proportion of axons with large myelin thickness than nerves from rats of 1P, 3P, or 12P litters. SUn of heaviest rats from 9P and 12P litters had greater CAP area and myelination than the lightest rats from the same litters. We propose that a complex interplay of sensory, social, and nutritional factors arising from mother and littermate interactions during the preweaning period influence myelination and the propagation of action potentials in the SUn of adult rats.

Neonatal ventral hippocampus lesion disrupts maternal behavior in rats: An animal model of schizophrenia.

Although individuals with schizophrenia typically present deficits in social interaction, little is known about the quality of their parent-infant interactions. In the present study, we assessed the behavioral effects of neonatal ventral hippocampus lesion (nVHL) in female rats (nVHL is known to induce schizophrenia-like deficits in males). Sexually naïve adult nVHL or sham female rats received cognitive and social tests, and their maternal behavior was observed in independent groups of adult nVHL and sham rats on postpartum days 2, 6, and 12. Compared to Sham females, naïve nVHL rats displayed elevated locomotor activity, less social interaction, and disrupted habituation of the acoustic startle response (ASR), while dorsal immobility (a defensive behavioral response) and prepulse inhibition of ASR were not affected. Although all nVHL mothers retrieved their pups, adopted the crouching posture, and nursed them, they showed disturbances in the display of pup body licking and nest building. Furthermore, a high proportion of nVHL mothers displayed atypical retrieval of pups and re-retrieving of pups, atypical nest-building, excavation, and cannibalism, as well a high level of these behaviors. These data indicate that cognition, locomotor activity, and maternal care is disrupted in nVHL female, suggesting disturbances in mesocorticolimbic dopaminergic systems and/or in social cognition.

Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock.

The mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

Physiological changes of growth hormone during lactation in pup rats artificially reared.

During the lactation period, rat pups are fed by the dam, and the patterns of mother-pup interaction change during this period. Additionally, there are changes in feeding; first, mother´s milk is the only food needed for sustenance, and later, it is combined with solid food and water. GH serum concentrations depend on both maternal-pup interaction and energy metabolism. In the artificial rearing (AR) procedure, pups are deprived of mother-pup interaction, and the feeding pattern is controlled. This rearing paradigm has been used in rats to analyze the effects of maternal deprivation on social behavior. In the present study, we analyzed the variation in GH, acylated ghrelin and IGF-1 serum concentrations throughout the lactation period in AR pups. At pnd7, the maternal rearing (MR) pups responded to a 4 h fast with a drop in GH serum concentration, which is a well-known response to maternal deprivation. GH serum levels in the AR pups did not change, suggesting an adaptation phenomenon. A dopamine inhibitory effect of GH secretion was observed in pnd7 cultured somatotropes, suggesting dopamine regulation of GH secretion at this age. Acylated ghrelin serum levels in the AR pups showed an inverted pattern compared to that in the MR pups, which was related to the artificial feeding pattern. IGF-1 serum levels were lower in the AR pups than in MR pups, which was associated with hepatic GH resistance and with low Igf1 mRNA expression at pnd7. Interestingly, at pnd14, both pup groups showed high hepatic Igf1 mRNA expression but low IGF-1 serum levels, and this was inverted at pnd21. However, serum glucose levels were lower in the AR pups at pnd14 but reached the same levels as the MR pups at pnd21. Moreover, hepatomegaly and higher hepatic GH-receptor levels were observed in the AR pups at pnd21, which was in agreement with an absence of a solid food meal. During AR, the pups lost the maternal interaction-stimulated GH secretion, which correlated with lower IGF-1 serum levels during the first week of postnatal development. Later, the AR pups exhibited hepatic responses, in order to satisfy the metabolic demand for the normal weaning, with low carbohydrates levels in their meal.

Maternal care activates the ventral tegmental area but not dopaminergic cells in the rat.

The ventral tegmental area (VTA), together with the preoptic area, is part of a neural circuit necessary for the expression of maternal behaviour (MB); destruction of either area disrupts MB in postpartum rats. Central to the proposal of VTA activation are dopaminergic cells, for which the cell bodies lie in the VTA and project to forebrain structures. This mesolimbic system is a motivational circuit involved in rewarding behaviours such as sex and MB. Despite their recognised importance, surprisingly, unlike the preoptic area, there are no anatomical descriptions of the pattern of VTA activation or of the dopaminergic cell activation, specifically in relation to MB in the rat. In the present study, we explore the possible activation (as indicated by Fos protein via immunohistochemistry) of the anterior and medial portions of the VTA and in the dopaminergic cells in these regions, as well as in the medial preoptic area, in lactating rats, at postpartum day 7 (after a 12-hour mother/pups separation), and in dioestrous females. After 12 hours, mothers were perfused at that moment or after a 90 minutes of interaction, or not, with their pups. We found a strong significant Fos induction in both the preoptic area and in the anterior portion of VTA in dams that interacted with their pups. The number of dopaminergic cells that coexpressed Fos did not differ across groups. Additionally, we determined Fos and GABA colocalisation in the anterior part of the VTA and found dense GABAergic processes, possibly varicosities, in the area of increased Fos expression. The results of the present study support a proposed GABAergic pathway from medial preoptic area to VTA cells, critical for the expression of MB. Future experiments are warranted to explore the neurochemical identity of the Fos and no-Fos expressing cells that are recipients of GABAergic processes in the VTA, aiming to better understand the neural circuitry of the VTA in relation to MB.

Early postnatal development of electrophysiological and histological properties of sensory sural nerves in male rats that were maternally deprived and artificially reared: Role of tactile stimulation.

Early adverse experiences disrupt brain development and behavior, but little is known about how such experiences impact on the development of the peripheral nervous system. Recently, we found alterations in the electrophysiological and histological characteristics of the sensory sural (SU) nerve in maternally deprived, artificially reared (AR) adult male rats, as compared with maternally reared (MR) control rats. In the present study, our aim was to characterize the ontogeny of these alterations. Thus, male pups of four postnatal days (PND) were (1) AR group, (2) AR and received daily tactile stimulation to the body and anogenital region (AR-Tactile group); or (3) reared by their mother (MR group). At PND 7, 14, or 21, electrophysiological properties and histological characteristics of the SU nerves were assessed. At PND 7, the electrophysiological properties and most histological parameters of the SU nerve did not differ among MR, AR, and AR-Tactile groups. By contrast, at PND 14 and/or 21, the SU nerve of AR rats showed a lower CAP amplitude and area, and a significant reduction in myelin area and myelin thickness, which were accompanied by a reduction in axon area (day 21 only) compared to the nerves of MR rats. Tactile stimulation (AR-Tactile group) partially prevented most of these alterations. These results suggest that sensory cues from the mother and/or littermates during the first 7-14 PND are relevant for the proper development and function of the adult SU nerve. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 351-362, 2018.

Disruption of behavior and brain metabolism in artificially reared rats.

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017.

Bidirectional Effects of Mother-Young Contact on the Maternal and Neonatal Brains.

Adaptive plasticity occurs intensely during the early postnatal period through processes like proliferation, migration, differentiation, synaptogenesis, myelination and apoptosis. Exposure to particular stimuli during this critical period has long-lasting effects on cognition, stress reactivity and behavior. Maternal care is the main source of social, sensory and chemical stimulation to the young and is, therefore, critical to "fine-tune" the offspring's neural development. Mothers providing a low quantity or quality of stimulation produce offspring that will exhibit reduced cognitive performance, impaired social affiliation and increased agonistic behaviors. Transgenerational transmission of such traits occurs epigenetically, i.e., through mechanisms like DNA methylation and post-translational modification of nucleosomal histones, processes that silence or increase gene expression without affecting the DNA sequence. Reciprocally, providing maternal care profoundly affects the behavior, learning, memory and fine neuroanatomy of the adult female. Such effects are in many cases permanent and sometimes they involve the hormones of pregnancy and lactation. The above evidence supports the idea that the mother-young dyad exerts profound and permanent effects on the brains of both adult and developing organisms, respectively. Effects on the latter can be explained by the neural developmental processes taking place during the early postnatal period. In contrast, little is known about the mechanisms mediating the plasticity of the adult maternal brain. The bidirectional effects that mother and young exert on each other's brains exemplify a remarkable plasticity of this organ for organizing itself and provide an immense source of variability for adaptation and evolution in mammals.

Deconstructing the function of maternal stimulation in offspring development: Insights from the artificial rearing model in rats.

This article is part of a Special Issue on "Parental Care". Maternal behavior has an important function in stimulating adequate growth and development of the young. Several approaches have been used in primates and rodents to deconstruct and examine the influence of specific components of maternal stimulation on offspring development. These approaches include observational studies of typical mother-infant interactions and studies of the effects of intermittent or complete deprivation of maternal contact. In this review, we focus on one unique approach using rats that enables the complete control of maternal variables by means of rearing rat pups artificially without contact with the mother or litter, while maintaining stable nutrition, temperature and exposure to stressful stimuli. This artificial rearing model permits the removal and controlled replacement of relevant maternal and litter stimuli and has contributed valuable insights regarding the influence of these stimuli on various developmental outcomes. It also enables the analysis of factors implicated in social isolation itself and their long-term influence. We provide an overview of the effects of artificial rearing on behavior, physiology, and neurobiology, including the influence of replacing maternal tactile stimulation and littermate contact on these outcomes. We then discuss the relevance of these effects in terms of the maternal role in regulating different aspects of offspring development and implications for human research. We emphasize that artificial rearing of rats does not lead to a global insult of nervous system development, making this paradigm useful in investigating specific developmental effects associated with maternal stimulation.

Role of sensory, social, and hormonal signals from the mother on the development of offspring.

For mammals, sensory, social, and hormonal experience early in life is essential for the continuity of the infant's development. These experiences come from the mother through maternal care, and have enduring effects on the physiology and behavior of the adult organism. Disturbing the mother-offspring interaction by maternal deprivation (neglect) or exposure to adverse events as chronic stress, maltreatment, or sexual abuse has negative effects on the mental, psychological, physiological, and behavioral health. Indeed, these kinds of negative experiences can be the source of some neuropsychiatric diseases as depression, anxiety, impulsive aggression, and antisocial behavior. The purpose of this chapter is to review the most relevant evidence that supports the participation of cues from the mother and/or littermates during the postnatal preweaning period for the development of nervous system of the offspring. These findings come from the most frequently utilized experimental paradigms used in animal models, such as natural variations in maternal behavior, handling, partial maternal deprivation, and total maternal deprivation and artificial rearing. Through the use of these experimental procedures, it is possible to positively (handling paradigm), or negatively (maternal deprivation paradigms), affect the offspring's development. Finally, this chapter reviews the importance of the hormones that pups ingest through the maternal milk during early lactation on the development of several physiological systems, including the immune, endocrine systems, as well as on the adult behavior of the offspring.

Early social isolation provokes electrophysiological and structural changes in cutaneous sensory nerves of adult male rats.

Sensory and social deprivation from the mother and littermates during early life disturbs the development of the central nervous system, but little is known about its effect on the development of the peripheral nervous system. To assess peripheral effects of early isolation, male rat pups were reared artificially in complete social isolation (AR); reared artificially with two same-age conspecifics (AR-Social); or reared by their mothers and with littermates (MR). As adults, the electrophysiological properties of the sensory sural (SU) nerve were recorded. We found that the amplitude and normalized area (with respect to body weight) of the compound action potential (CAP) response provoked by single electrical pulses of graded intensity in the SU nerves of AR animals were shorter than the CAP recorded in SU nerves from MR and AR-Social animals. The slope of the stimulus-response curve of AR SU nerves was smaller than that of the other nerves. The histological characterization of axons in the SU nerves was made and showed that the myelin thickness of axons in AR SU nerves was significant lower (2-7µm) than that of the axons in the other nerves. Furthermore, the area and axon diameter of SU nerves of both AR and AR-Social animals were significant lower than in MR animals. This is the first report to show that maternal and littermate deprivation by AR disturbs the development of the myelination and electrophysiological properties of axons in the SU nerve; the replacement of social cues prevents most of the effects.

Rearrangement of the dendritic morphology of the neurons from prefrontal cortex and hippocampus after subthalamic lesion in Sprague-Dawley rats.

Several studies in rodents have suggested the inactivation of the subthalamic nucleus (STN) as an alternative strategy to Parkinson's disease (PD) treatment. The STN is part of the basal ganglia and plays an important role in the motor function; however, recent data suggest that this structure has a critical role in the cognitive function of the limbic system. The STN receives direct projection from the prefrontal cortex (PFC), structure interconnected with the hippocampus and both structures send excitatory projections to the nucleus accumbens (NAcc). Here, we determined whether and which changes occurred 4 weeks after a STN lesion in the dendritic morphology of pyramidal neurons of the layers 3 and 5 of the PFC and basolateral amygdala, neurons of the ventral hippocampus, and the medium spiny neurons of the NAcc and caudate-putamen. Dendritic morphology was measured using the Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of STN lesion on locomotor behavior assessed by an open field test, social interaction, acoustic startle response, prepulse inhibition, and locomotor activity induced by a novel environment and amphetamine. We found that STN damage induced a deficit in locomotion measured by open field test with neuronal hypertrophy in PFC (layer 5) and reduced spinogenesis in CA1 ventral hippocampus and PFC (layer 3). Taken together, these data suggest that the behavioral and morphological effects of STN lesion are, at least partially, mediated by limbic subregions with possible consequences for cognitive-related behaviors observed in PD treatment.

Artificial feeding synchronizes behavioral, hormonal, metabolic and neural parameters in mother-deprived neonatal rabbit pups.

Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study, we hypothesized that food is the main entraining signal. Using mother-deprived pups, we tested the effects of artificial feeding on the synchronization of locomotor behavior, plasma glucose, corticosterone, c-Fos (FOS) and PERIOD1 (PER1) rhythms in suprachiasmatic, supraoptic, paraventricular and tuberomammillary nuclei. At postnatal day 1, an intragastric tube was placed by gastrostomy. The next day and for the rest of the experiment, pups were fed with a milk formula through the cannula at either 02:00 h or 10:00 h [feeding time = zeitgeber time (ZT)0]. At postnatal days 5-7, pups exhibited behavioral arousal, with a significant increase in locomotor behavior 60 min before feeding. Glucose levels increased after feeding, peaking at ZT4-ZT12 and then declining. Corticosterone levels were highest around the time of feeding, and then decreased to trough concentrations at ZT12-ZT16, increasing again in anticipation of the next feeding bout. In the brain, the suprachiasmatic nucleus had a rhythm of FOS and PER1 that was not significantly affected by the feeding schedule. Conversely, the supraoptic, paraventricular and tuberomammillary nuclei had rhythms of both FOS and PER1 induced by the time of scheduled feeding. We conclude that the nursing rabbit pup is a natural model of food entrainment, as food, in this case milk formula, is a strong synchronizing signal for behavioral, hormonal, metabolic and neural parameters.

Comparative analysis of maternal care in the high-yawning (HY) and low-yawning (LY) sublines from Sprague-Dawley rats.

High- and low-yawning rats (HY and LY) were selectively bred as a function of their spontaneous yawning frequency with the LY subline about 2 yawns/hr and the HY 20 yawns/hr. The HY rats have more grooming bouts and travel longer distances in an open field. HY dams spent less time in the nest, retrieved their pups faster, and show a longer latency to licking and mouthing the pups than the LY or outbred Sprague-Dawley (SD) animals. The percentage of HY dams that had atypical retrieving was higher, with a lower nest quality, and produced offspring whose weights were lower than those from the LY subline. We also showed that the pregnant HY dams have fewer pups and the percentage that had lost at least three pups during lactation was higher than the SD and LY dams. In conclusion, HY dams are motivated to take care of their pups, but the "fine tuning" of maternal care is disturbed.

Communication by olfactory signals in rabbits: its role in reproduction.

Rabbits use a variety of olfactory signals to transmit information related with reproduction. Such cues are produced in skin glands (submandibular, anal, Harder's, lachrymal, preputial) and the mammary gland-nipple complex. Some signals are transmitted by active behaviors, for example, chin-marking, urination, and defecation, while others are transmitted passively (e.g., mammary pheromone (MP) and inguinal gland secretions). We show that sex steroids regulate: chinning frequency and the chin gland's size, weight and secretory activity in bucks and does by acting on specific brain regions or on the chin gland, respectively. The "mammary pheromone," identified in milk as 2-methyl-but-2-enal, is essential for guiding the pups to the nipples, but its origin (mammary gland, ventral skin, nipple) remains to be determined. Estradiol, progesterone, and prolactin regulate the emission of an olfactory cue that also triggers nipple-search behavior in the pups, but its chemical identity and relation with the MP are unclear.

Effects of prolactin deficiency during the early postnatal period on the development of maternal behavior in female rats: mother's milk makes the difference.

During early life, prolactin (PRL) ingested by the pups through the milk participates in the development of neuroendocrine, immunological and reproductive systems. The present study tested whether a deficiency in PRL in the dam's milk during early lactation affected the offspring in terms of the maternal responsiveness in the sensitization paradigm and behavioral response to a novel environment in the offspring. Thus, lactating rats were injected (sc) on postnatal days (PND) 2-5 with bromocriptine (125 microg/day), bromocriptine+ovine PRL (125 microg+300 microg/day), or vehicle. As juveniles (at PND 24) or adults (PND 90-100), one female from each litter was exposed to 5 foster pups continuously for 8 days and their maternal responsiveness was recorded. Female offspring were also tested in an open field arena. Adult, but not juvenile, female offspring of bromocriptine-treated mothers showed an increased latency to become maternal, in comparison to latencies displayed by the offspring of control mothers. Furthermore, the proportion of adult, but not juvenile, offspring of bromocriptine-treated mothers that became maternal was lower than that showed by the offspring of vehicle-treated mothers. In comparison to female offspring of vehicle-treated mothers, female offspring of bromocriptine-treated mothers spent less time hovering over the pups (as juvenile females), body licking (as both juvenile and adult females), and in close proximity to pups (as adult females) during the maternal behavior test. Simultaneous administration of ovine PRL and bromocriptine reversed almost all the negative effects of bromocriptine. These data suggest that maternally-derived PRL participates during the early postnatal period in the development of neural systems that underlie the control of maternal behavior.

Maternal and peer contact during the postnatal period participate in the normal development of maternal aggression, maternal behavior, and the behavioral response to novelty.

In the rat, social isolation during the early postnatal period disrupts the adult function of certain neuroendocrine and neurobehavioral systems. In the present study, we assessed the effects of peer and maternal contact during this period on the adult expression of aggression, maternal behavior, and the behavioral response to novelty. Female rat pups of the Wistar strain were reared across postnatal days 3-19 in one of the following conditions: (1) by their mother and with littermates (MR, control); (2) artificially reared in complete social isolation (AR); or (3) artificially reared in the presence of two same-age conspecifics (AR-Soc). As adults, all females were administered a resident-intruder aggression test, first in a non-maternal context ("territorial" aggression) and then in the presence of their pups ("maternal" aggression). Additionally, their maternal behavior and response to a novel object placed in a familiar open field arena were quantified. We found that maternal isolation impaired maternal behavior, increased maternal aggression, and increased the olfactory investigation of a novel object. The presence of peers prevented the effect of artificial rearing on aggression, but not its effects on maternal behavior or response to novelty. In the maternal aggression test, AR-Soc females engaged in significantly more sniffing of the intruder compared to the other two groups. The present results confirm and extend those of previous studies in a different strain (Sprague-Dawley), and indicate that peer-derived stimuli impact on the development of neurobehavioral systems underlying aggressive and non-aggressive social interactions, whereas the normal development of maternal behavior and response to novelty requires maternally derived stimuli.