The effects of early isolation on sexual behavior and c-fos expression in naïve male Long-Evans rats

Previous findings have demonstrated that the maternal environment is important for the development of male sexual behavior. The present study examined the effects of complete early life isolation and replacement 'stroking' stimulation on male sexual behavior and neural activation as seen by Fos immunoreactivity (Fos-IR). Animals were either artificially reared (AR) with minimal (AR-MIN) or maximal (AR-MAX) body simulation, or maternally reared (MR). In adulthood, animals were either given an exposure to an estrous female (EXP) or left undisturbed (NoEXP). No significant effects of early development were found in sexual behavior; however differences in activation in response to this exposure were observed. AR-MIN animals showed lower Fos-IR in the medial preoptic area and the ventromedial hypothalamus compared to MR animals. AR-MAX animals were not significantly different from either condition. These findings demonstrate that although there are no differences in the quality of the first copulatory exposure between AR and MR animals, the brain's response to this exposure differs in sites within the brain that subserve sexual behavior.     

Experience-dependent cell survival in the maternal rat brain

Postpartum maternal experience produces long-lasting changes in maternal behavior in the mother rat, which can be altered by early-life isolation. Postpartum experience also affects the regulation of adult neurogenesis in the neural circuit underlying maternal behavior, in a region-specific manner. Female rats were reared either with their mothers (MR) or in isolation in an artificial rearing (AR) paradigm. In adulthood, rats were mated and separated from their pups at birth. The following day, dams were injected with a mitotic marker and either allowed to interact with pups (maternal experience) or left alone. Results show that MR rats that acquire a later maternal experience show increases in cell survival in parts of the excitatory limb of the maternal neural network (bed nucleus of the stria terminalis and nucleus accumbens), but no changes in the inhibitory limb (amygdala). In comparison to AR inexperienced rats, AR maternally experienced rats show no increases in cell survival in the excitatory limb, but a striking reduction in cell survival in the inhibitory limb. The results suggest that early preweaning maternal isolation alters the structural plasticity that occurs following a postpartum maternal experience.     

Maternal and littermate deprivation disrupts maternal behavior and social-learning of food preference in adulthood: tactile stimulation, nest odor, and social rearing prevent these effects

Maternal and littermate (social) separation, through artificial rearing (AR), disrupts the development of subsequent maternal behavior and social learning in rats. The addition of maternal-licking-like stimulation during AR, partially reverses some of these effects. However, little is know about the role of social stimuli from littermates and nest odors during the preweaning period, in the development of the adult maternal behavior and social learning. The purpose of this study was to examine the effects of peer- and peer-and-odor rearing on the development of maternal behavior and social learning in rats. Female pups were reared with mothers (mother reared-MR) or without mothers (AR) from postnatal day (PND) 3. AR rats received three different treatments: (1) AR-CONTROL group received minimal tactile stimulation, (2) AR-ODOR females received exposure to maternal nest material inside the AR-isolation-cup environment, (3) AR-SOCIAL group was reared in the cup with maternal nest material and a conspecific of the same-age and same-sex and received additional tactile stimulation. MR females were reared by their mothers in the nest and with conspecifics. In adulthood, rats were tested for maternal behavior towards their own pups and in a social learning task. Results confirm our previous report that AR impairs performance of maternal behavior and the development of a social food preference. Furthermore, social cues from a littermate, in combination with tactile stimulation and the nest odor, reversed the negative effects of complete isolation (AR-CONTROL) on some of the above behaviors. Exposure to the odor alone also had effects on some of these olfactory-mediated behaviors. These studies indicate that social stimulation from littermates during the preweaning period, in combination with odor from the nest and tactile stimulation, contributes to the development of affiliative behaviors.     

Relationships between maternal behavior of SHR and WKY dams and adult blood pressures of cross-fostered F1 pups

In this experiment SHR and WKY dams reared genetically identical F1 pups derived from SHR x WKY matings. We found that a composite maternal behavior score was positively correlated with adult blood pressures of the fostered offspring. This replicated a similar finding from our previous study in which SHR and WKY mothers reared their own pups. Unlike this previous study, WKY dams rearing F1 pups exhibited maternal behavior patterns similar to SHR dams. Finally, we found there was no effect of the strain of foster mother upon adult blood pressures of the F1 offspring. These results indicate that some aspects of maternal behavior may change as a function of pup characteristics, and support our hypothesis that the cardiovascular system may be shaped by experiences of early life which are embedded in mother/young behavioral interactions.     

Complete maternal deprivation affects social, but not spatial, learning in adult rats

The effects of maternal deprivation on learning of social and spatial tasks were investigated in female adult rats. Pups were reared artificially and received "lickinglike" tactile stimulation (AR animals) or were reared with their mothers (MR animals). In adulthood, subjects were tested on paradigms of spatial learning and on paradigms involving learning of social cues. Results showed that maternal deprivation did not affect performance on spatial learning, but it did impair performance on the three social learning tasks. The AR animals made no distinction between a new and a previously presented juvenile conspecific. AR animals also responded less rapidly than MR animals at test for maternal behavior 2 weeks after a postpartum experience with pups. Finally, AR animals did not develop a preference for a food previously eaten by a familiar conspecific whereas MR animals did. This study indicates that animals reared without mother and siblings show no deficits in spatial tasks while showing consistent deficits in learning involving social interactions.     

Artificial rearing causes changes in maternal behavior and c-fos expression in juvenile female rats

This study investigated the effects of early-rearing experiences on responsiveness to pups and on the pattern of c-fos activation in the brain of juvenile female rats. From Days 4 to 20, littermate females were reared with their mothers (MR) or artificially (AR). AR rats received minimal licking-like tactile stimulation (AR-min) or maximal stimulation (AR-max). On Day 20, rats were exposed to pups for 4 or 8 days, exposed to a playmate for 4 or 8 days, or left in isolation for 4 or 8 days. Compared with MR rats, pup-exposed AR rats engaged in less pup licking, and all AR rats showed significant reductions in c-fos immunoreactivity in the medial preoptic area and the parietal and piriform cortices. The AR-min group showed the greatest difference in Fos-lir compared with the MR groups. Possible mechanisms that mediate the effects of rearing on the development of neural circuits underlying maternal behavior are discussed.     

Long-term effects of differential early rearing in rhesus macaques: behavioral reactivity in adulthood

Adverse early experiences are associated with a range of deleterious health outcomes in humans, including higher risk for affective disorders. Studies using a long-standing model of nonhuman primate model of early adversity have demonstrated that nursery-reared (NR) monkeys exhibit alterations in multiple aspects of biobehavioral development; however, few studies have evaluated the persistence of socioaffective behavioral changes through adulthood. We evaluated the effects of early rearing experience on adult animals' response to a well-validated assessment of anxiety-like behavior, the human intruder paradigm (HIP). We tested 22 rhesus monkeys who were either nursery-reared (NR) or reared with their mothers (mother-reared; MR). NR monkeys were inhibited in their behavior compared to MR monkeys, with reduced locomotion and exploratory behaviors. NR animals showed a marginal increase in freezing. Together these findings demonstrate that the consequences of differential infant rearing experience on socioaffective behavior persist into adulthood, with evidence of greater inhibition in NR monkeys.     

Early-life maternal separation and social isolation produce an increase in impulsive action but not impulsive choice

Early life environment, events, and context, such as mother-offspring relationship, can have profound effects on future behavior and physiology. We investigated the effects of long-term maternal and social separation, through artificial rearing, on adult impulsivity. Rats were maternally reared (MR) or artificially reared (AR) and half of the AR rats were provided with replacement somatosensory stimulation intended to simulate maternal licking. There are at least 2 forms of impulsivity and we compared rats on 1 test of impulsive action (differential reinforcement of low rates of responding-DRL-20s) and 2 tests of impulsive choice (delay discounting and fixed consecutive number schedule-FCN). We found that AR rats are more action impulsive; however, this effect can be reduced by maternal licking-like stimulation. In contrast, AR rats did not display an increase in impulsive choice. Overall, these experiments show that early life maternal and social separation have different effects on the 2 forms of impulsivity.     

Impact of mothers’ experience and early-life stress on aggression and cognition in adult male mice

The postnatal period is important for brain development and behavioral programming. Here, we hypothesized that females’ stressful experience early in life can lead to disruption of mother–offspring interactions with their own progeny. The objective of this study was to assess the effects of mothers’ stressful experience, early-life stress, or both on the behavior of adult male mice. In this study, female mice were allowed to raise their pups either without exposure to stress (normal rearing conditions, NC) or with exposure to maternal separation (3 hr/day, maternal separation, MS). Adult F1 female mice who had experienced MS (stressed mothers, SM) or had been reared normally (undisturbed mothers, UM) were used for generating F2 offspring, which was then exposed (or not exposed) to early-life stress. We assessed anxiety-like behavior, exploratory activity, locomotor activity, aggression, and cognition in four groups of adult F2 males (UM+NC, UM+MS, SM+NC, and SM+MS). We found that SM+MS males become more aggressive if agonistic contact is long enough; these results point to a change in their social coping strategy. Moreover, these aggressive males tended to show better long-term spatial memory. Overall, our findings suggest that mothers’ early-life experience may have important implications for the adult behavior of their offspring.     

Early experience and maternal behavior in rats

This study examined the effects of early experience (early weaning with group housing in sibling groups (EG), or early weaning plus social isolation (EI) from 14 to 24 days of age) on maternal, play, and social behaviors expressed during 5 days of sensitization at 24 days, and then later at 100 days of age. Our results showed that maternal behaviors at 24 days could be altered by these early experiences. At 24 days of age fewer EI animals retrieved compared with normally weaned controls (NW), but more showed play behavior in the presence of pups. EG animals showed intermediate levels of retrieving relative to NW controls, and no concomitant changes in play behaviors. When retested as adults, females in all groups showed similar levels of all maternal behaviors. But EI adults of both sexes showed persistent intrusion of play behaviors, and higher levels of rearing and undirected activity in the presence of neonates. Factor analyses revealed that previously sensitized adult males showed patterns of organization of maternal behaviors that resembled adult females rather than those shown by control males reared without sensitization experience. Previously sensitized females also showed a retention of the play behavior patterns characteristic of juveniles, not present in females without sensitization experience. These results show that social experience during the weaning period can affect the development of maternal and play behavior elicited by neonates during the juvenile period that persist into adulthood, and the juvenile sensitization experience exerts longterm effects on adult patterns of maternal behavior in both sexes.     

Cocaine treatment and prenatal environment interact to disrupt intergenerational maternal behavior in rats

The link between impaired maternal behavior (MB) and cocaine treatment could result from drug-induced decreases in maternal reactivity to offspring, prenatal drug exposure (PDE) in offspring that could alter their ability to elicit MB, or the interaction of both, which could subsequently impair MB of the 1st-generation dams. Following chronic or intermittent cocaine or saline treatment during gestation, rat dams rearing natural or cross-fostered litters were compared along with untreated dams for MB. Untreated 1st-generation females with differentially treated rearing dams and PDE were tested for MB with their natural litters. The authors report disruptions in MB in dams and their 1st-generation offspring, attributable to main and interaction effects of maternal treatment, litter PDE, and rearing experience.     

Programming life histories: Effects of maternal and environmental variables upon open-field behavior

Open-field behavior was studied as a function of three classes of variables: maternal characteristics, rearing environment, and sexual experience. Mothers of experimental subjects were either handled or nonhandled in infancy. Subjects were born and reared to weaning either in maternit cages or in Hebb-type free environments and were placed after weaning into either a laboratory cage or free enviroment. Sexual experience consisted either of bearing and raising a litter or no sexual experience. The results confirmed previous findings that offspring of mothers handled in infancy arc significantly less active in the open field than the offspring of nonhandled mothers. The maternal handling variable also interacted significantly with breeding experience: for rats which had not been bred, those raised by nonhandled mothers were more active than those raised by handled mothers; for females with breeding experience the reverse was true. Overall, thosc femalcs which had reared a litter were more active and defecated more than their nonbred littermates.     

Overlapping litters in rats: effects on maternal behavior and offspring emotionality

Female rats have a fertile postpartum estrus, which can result in a simultaneous gestation and lactation and later in the overlapping of two different-age litters. These different physiological and contextual situations may affect the maternal behavior of lactating rats and provoke long-lasting changes in the affective behavior of the litter. Therefore, we aimed to assess the effect of pregnancy and of litter overlapping on the maternal behavior of lactating rats and to describe the maternal- and anxiety-like behaviors of the juveniles that remained in contact with their younger siblings. Results showed that pregnant lactating rats spent more time outside the nest and less time nursing than non-pregnant mothers. On the other side, mothers with overlapping litters licked less the newborn pups than mothers with single litters. These deficits in maternal licking received by neonates were overridden by the juveniles' licking behavior to their younger siblings. Adult male and diestrous female rats reared with younger siblings showed a reduced anxiety-like behavior as compared to age-weaning matched animals without this experience. Thus, natural changes in the reproductive conditions and in the early experience, affect the maternal behavior and long-term modulate affective behavior of the individuals.     

Genetic and littermate influences on yawning in two selectively bred strains of rats

This study was made to separate genetic from postnatal maternal influences on yawning in two strains of Sprague‐Dawley rats selected for high‐ (HY) and low‐yawning frequency (LY). Foster mothers of the two strains reared litters of pups in the four possible combinations and yawning was recorded in a novel environment when the adult offspring were 75‐day‐old. Yawning frequency of males and females was affected by pup strain but not by the strain of the foster mothers, when litter size was made constant; HY adult offspring yawned more than LY adult offspring. Yawning frequency was higher in HY male offspring than in HY female offspring. An interaction term between pup sex and the strain of the foster mothers revealed that while males reared by LY mothers yawned more than males reared by HY mothers, females reared by HY mothers yawned more than females reared by LY mothers. Mean frequency of yawning increased with the sex ratio of HY litters. These findings indicate that genetic and genotype‐correlated littermate effects influence yawning frequency of adult offspring in response to a novel environment. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 51: 243–248, 2009     

Early maternal rejection and later social anxiety in juvenile and adult Japanese macaques

This study investigated the relationships between early maternal style and subsequent juvenile and adult behavior of offspring in Japanese macaques (Macaca fuscata). Early maternal style had no effect on baseline behavior of offspring when adult. In contrast, early maternal style was correlated with the response of adult offspring to stressful social interactions, and particularly with their response to actual or potential aggression. Infants whose mothers encouraged more independence showing high rates of rejection were less fearful and did cope better with stressful situations when adult. Although based on correlational data, these results suggest that in macaques maternal rejection can promote offspring independence and the development of a less anxious personality.     

Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity

BackgroundIn the present study, we tested both the cumulative stress and the mismatch hypothesis of psychopathology. For this purpose the combined effects of early-life adversity and later-life stress exposure on behavioral markers of psychosis susceptibility were studied in male Wistar rats.MethodExperiment I: rat pups divided on the basis of the levels of their maternal care experience in low, medium or high maternal care groups, were reared post-weaning in groups (Exp. IA) or in social isolation (Exp. IB) and tested at adulthood under basal conditions or after an acute corticosterone (CORT) administration. Maternal care levels were assessed by measuring the dam's licking and grooming (LG) the first postnatal week of life.Experiment II: rat pups exposed as neonates to daily sessions of 8 h of maternal separation (MS) on postnatal days 3, 4 and 5 either altogether in their home cage (HOME SEP) or alone in a novel environment (NOVEL SEP), were reared post-weaning in groups and tested at adulthood under basal conditions.Adult testing included behaviors marking psychosis susceptibility: apomorphine-induced gnawing (APO-gnawing), acoustic startle response and its modulation by a prepulse stimulus (PPI). The behavior of the Medium LG offspring was used as baseline reference for all the three experiments.ResultsExperiment I: Low maternal LG history alone had limited effects on the behavior of Wistar offspring, although increased acoustic startle and increased PPI, at high prepulse intensity levels, were observed. When low maternal LG history was combined with post-weaning social isolation, basal APO-gnawing was decreased and PPI increased, compared to High LG and Med LG offspring. This reflects attenuated psychosis susceptibility. High LG offspring reared in isolation displayed, however, the highest APO-gnawing and the lowest PPI levels among rats reared in social isolation, which is indicative for increased psychosis susceptibility. These findings support the mismatch hypothesis. For demonstration of the cumulative stress hypothesis an injection of CORT in the adult Low LG offspring was required that increased APO-gnawing and reduced PPI. This CORT-induced PPI disruption was greatly enhanced after additional isolation rearing. The High LG group, either socially housed or reared in isolation, was resistant to the acute effects of CORT at adulthood.Experiment II: MS increased psychosis susceptibility only in NOVEL SEP rats that had experienced MS in the context of early social isolation. These individuals displayed increased adult APO-gnawing and reduced PPI, if reared post-weaning in a condition that does not match with their early life social environment (i.e. group housing). This finding supports the mismatch hypothesis.ConclusionThe outcome of environmental manipulations on developmental programming of psychosis susceptibility depends on the interplay of early-life adversity and later-life stressors in a manner that supports the mismatch hypothesis. However, evidence for the cumulative stress hypothesis arises if vulnerable individuals are exposed in later life additionally to excess of the stress hormone CORT.     

Postnatal effects on reproduction and maternal care in early- and late-maturing gerbils

In previous papers, we have identified a number of differences in both the reproductive profiles and patterns of maternal care shown by female gerbils exhibiting vaginal opening either before or after weaning. Early-maturing females delivered their first litters when younger, produced a greater percentage of female offspring/litter, and a greater percentage of early-maturing daughters than late-maturing females. Further, early-maturing females exhibited reduced levels of maternal care, as assessed by time spent nursing, time pups were gathered in the nest, and probability of retrieval of displaced young. In the present experiments, we found that equating age at first parity of early- and late-maturing females (Experiment 1) eliminated differences between them in pup gathering, but not in pup retrieval or nursing. Further, equating age at first parity affected neither sex-ratios of litters at birth nor rate of maturation of daughters. Equating litter size at birth, sex-ratio of litters at birth, and maternal age at first parturition (Experiment 2) eliminated differences in the nursing behavior of early- and late-maturing females and reduced differences in retrieval behavior, but left rate of maturation of daughters unaffected. Last (Experiment 3), both daughters born to early-maturing females, reared by late-maturing females, and daughters born to late-maturing females, reared by early-maturing females, exhibited rates of maturation typical of daughters reared by their natural mothers.     

Mother - infant interactions: Effects of early handling of offspring on rat mothers' open-field behavior

Two experiments studied the open-field behaviors of rat mothers as a function of offspring manipulation. In the first experiment mothers whose offspring were “handled” were compared with mothers whose offspring were not handled. Mothers of handled offspring were found to be less emotional in the open field than control mothers. In the second experiment control litters and litters handled during their first week were fostered to mothers of nonhandled litters. The foster mothers and their new litters were not disturbed again until weaning 2 weeks later. Again, mothers which reared handled litters were less emotional than those which reared nonhandled litters. It was concluded that mothers are affected by early handling of their offspring, that the direction of influence can be from infant to mother, and that the effects of mother-infant interactions are likely to be extremely complex.     

Early maternal care predicts reliance on social learning about food in adult rats

Many vertebrates rely extensively on social information, but the value of information produced by other individuals will vary across contexts and habitats. Social learning may thus be optimized by the use of developmental or current cues to determine its likely value. Here, we show that a developmental cue, early maternal care, correlates with social learning propensities in adult rodents. The maternal behavior of rats Rattus norvegicus with their litters was scored over the first 6 days postpartum. Rat dams show consistent individual differences in the rate they lick and groom (LG) pups, allowing them to be categorized as high, low, or mid‐LG mothers. The 100‐day old male offspring of high and low‐LG mothers were given the opportunity to learn food preferences for novel diets from conspecifics that had previously eaten these diets (“demonstrators”). Offspring of high‐LG mothers socially learned food preferences, but offspring of low‐LG mothers did not. We administered oxytocin to subjects to address the hypothesis that it would increase the propensity for social learning, but there were no detectable effects. Our data raise the possibility that social learning propensities may be both relatively stable throughout life and part of a suite of traits “adaptively programmed” by early developmental experiences. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 168–175, 2013     

Prenatal and postnatal maternal contributions in the infection model of schizophrenia

Epidemiological studies have indicated that the risk of schizophrenia is enhanced by prenatal maternal infection with viral or bacterial pathogens. Recent experimentation in rodents has yielded additional support for a causal relationship between prenatal immune challenge and the emergence of psychosis-related abnormalities in brain and behaviour in later life. However, little is known about the putative roles of maternal postnatal factors in triggering and modulating the emergence of psychopathology following prenatal immunological stimulation. Here, we aimed to dissect the relative contributions of prenatal inflammatory events and postnatal maternal factors in precipitating juvenile and adult psychopathology in the resulting offspring with a cross-fostering design. Pregnant mice were exposed to the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 5 mg/kg, intravenously), or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were then simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. Prenatal PolyI:C administration did not affect the expression of latent inhibition (LI) at a juvenile stage of development, but led to the post-pubertal emergence of LI disruption in both aversive classical and instrumental conditioning regardless of the postnatal rearing condition. In addition, deficits in conditioning as such led to a pre- and post-pubertal loss of LI in prenatal control animals that were adopted by PolyI:C-treated surrogate mothers. Our findings thus indicate that the adoption of prenatally immune-challenged neonates by control surrogate mothers does not possess any protective effects against the subsequent emergence of psychopathology in adulthood. At the same time, however, the present study highlights for the first time that the adoption of prenatal control animals by immune-challenged rearing mothers is sufficient to precipitate learning disabilities in the juvenile and adult offspring.