Prenatal stress affects mother-infant interaction in Norway rats

Pregnant Long-Evans rats were stressed by crowding, and subsequent mother-infant interactions were described after cross-fostering. Prenatally stressed pups elicited less maternal licking from unstressed foster dams than controls, and previously stressed dams licked unstressed foster pups less than controls. No other differences in mother-infant interactions were detected. Adult offspring reared by foster dams that were stressed during pregnancy were more active in an open field than controls, but prenatally stressed and unstressed animals reared by control dams did not differ. Thus, stress during pregnancy can alter the maternal behavior of stressed dams, and the differential maternal stimulation can affect adult open-field behavior. Because prenatally stressed pups elicit different maternal care, cross-fostering does not eliminate the possibility that maternal stimulation may mediate some prenatal stress effects.     

Uterine positions and schedules of urination: correlates of differential maternal anogenital stimulation

Lactating Mongolian gerbils, like lactating Norway rats, reliably lick some pups in their litters more than they lick others. Male gerbil pups are licked more by their dams than are their sisters and some males and some females within each litter are licked more often than are their sibs of the same sex. In the present article, we explore the characteristics of same-sex littermates that are correlated with elicitation of extreme amounts of maternal anogenital licking. We found that both the male pup and the female pup in a litter of gerbils that received the most maternal anogenital licking: (1) released greater quantities of urine and (2) exhibited longer latencies to begin to urinate in response to artificial anogenital stimulation than did the male pup and the female pup in a litter that received the least amount of maternal anogenital licking. We also found that foster mothers rearing Caesarean-delivered litters spent more time licking the anogenital areas of: (1) those male pups that, as fetuses, had occupied uterine locations adjacent to relatively few females and (2) those female pups that, as fetuses, had occupied uterine locations adjacent to relatively many males. We discuss implications of these findings for understanding of how maternal behavior may mediate hormonal effects on the development of young gerbils.     

Mother-infant interactions in two strains of rats: Implications for dissociating mechanism and function of a maternal pattern

Mother-infant interaction was observed in Long-Evans and Fischer 344 rats after fostering within or across strains. Interactions immediately following introduction of foster pups to the cage as well as undisturbed interactions with resident litters were examined. Some differences were related to alien status, some to strain of pups, and others to strain of dams. Greater responsiveness to pups of the maternal strain was exhibited in retrieval and body licking. Long-Evans pups received more crouching from dams of both strains 3-12 days postpartum, perhaps because they are significantly larger. Regardless of pup strain, Long-Evans dams engaged in more maternal licking than did F344 dams, and this was more likely directed to the anogenital region. Dams of both strains were more likely to lick male than female pups, regardless of pup strain. The strain difference in maternal licking is consistent with adult strain differences in water and salt appetite and may contribute developmentally to the superior copulatory performance of Long-Evans males. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 310–312, 1997     

Maternal licking by virgin and lactating rats: water transfer from pups

Rat dams provide water to their young via milk. Dams reclaim much of this water by licking the pups' anogenital areas, stimulating reflexive urination and consuming the pups' urine. Sensitized virgin rats, induced to act maternally do not provide water to pups, but they nevertheless lick them. To determine whether bidirectional transfer of water between the rat mother and her litter mediates maternal licking, water transfer from pups to sensitized virgins was compared with that to lactating dams. We used time-lapse video recordings to measure anogenital licking of pups. Sensitized virgins and lactating dams spent equivalent amounts of time licking the anogenital regions of test litters. We quantified the amount of water transferred from offspring to both virgins and dams by injecting pups with tritiated water and measuring the radioactive label in maternal plasma after interaction with a litter of 5-day-olds. Dams obtained more than twice as much urine from the litter in 4 hr than did the maternal virgins. Differences in the amount of water obtained from pups were due to differences in urine availability caused by the receipt of milk from the dams. When the dams' nipples were ligated, so that their pups received no milk, ligated dams and virgins consumed equivalent amounts of pup urine. Maternal licking and urine consumption are not dependent solely upon the bidirectional exchange of water between the dam and her offspring.     

Effects of stress during pregnancy on maternal behavior in mice

The effects of stress experienced during pregnancy and raising stressed offspring on maternal behavior were investigated in Swiss-Webster mice. Dams were either stressed or not stressed during pregnancy, and raised either prenatally stressed or nonstressed cross-fostered pups. Maternal behaviors such as grooming, nursing, pup retrieval and maternal aggression were assessed during the first 4 days after birth. Nonstressed dams raising stressed pups and stressed dams raising nonstressed pups groomed and nursed their pups significantly less than did control dams (stressed dams raising stressed pups and nonstressed dams raising nonstressed pups). Nonstressed dams raising stressed pups were also the slowest to retrieve both the first and last pup in retrieval tests. Nonstressed dams raising nonstressed pups were significantly less aggressive than other dams. In contrast, stressed dams raising stressed pups exhibited high levels of nursing and grooming, retrieved their pups rapidly and were very aggressive towards an intruder. These results indicate that raising stressed pups, or experiencing stress during a pregnancy can have significant effects on maternal behaviors. Stressed dams raising stressed pups exhibit maternal care comparable to that of nonstressed dams raising nonstressed pups at least for nesting/nurturing behaviors, and show increased levels of aggression and pup retrieval.     

Effects of social stress and intrauterine position on sexual phenotype in wild-type house mice (Mus musculus)

Wild-type house mice were used to test the effect of intrauterine position on anogenital distance (AGD) and to verify whether crowding stress would masculinize female pups, developing at all intrauterine positions, as has been demonstrated in CF-1 mice stressed by restraint, heat, and light. Stress of crowding was documented by comparing aggressive behavior, litter birth weights, and plasma corticosterone levels among females in different densities. AGDs were recorded from pups born to females housed from day 12 to 19 of gestation either individually with their mate (nonstressed) or in one of two group-housed densities. Female pups from nonstressed dams positioned between two males in utero (2M females) had longer AGDs than females positioned between two females (0M females). AGDs of males from nonstressed dams did not differ on the basis of intrauterine position. Group-housed pregnant females in the higher of two densities had female pups with longer AGDs than female pups of other dams. However, variance in female pup AGD was no different among dams in different densities. These results extend to the wild house mouse previous findings in albino mice that intrauterine position influences sexual phenotype. In addition, social stress can induce masculinization of female pups in wild mice as physical stress has been shown to do in albinos. This suggests that intrauterine position effects and their modification by crowding stress can potentially influence the dynamics of wild house mouse populations.     

Maternal contributions to the development of masculine sexual behavior in laboratory rats

Maternal licking was manipulated by lining the nasal passages of rat dams with polyethylene tubing to interfere with their olfactory competence. Olfactory cues from pups elicit maternal licking and handling, particularly of anogenital regions, and dams with olfactory deficits were observed to lick their pups less. Mature male and female offspring of these dams and their controls were gonadectomized, treated with testosterone propionate, and tested for masculine sexual behavior. The male offspring of dams that provided less maternal licking had longer ejaculatory latencies, longer post-ejaculatory intromission latencies, and longer inter-intromission intervals than controls. Female offspring of the intubed dams performed fewer mounts and intromissions, had longer intromission latencies, and longer inter-intromission intervals. It was concluded that stimulation from maternal licking contributes toward the development of a mechanism that underlies the timing of copulatory rate.     

Effects of prenatal stress on sexual partner preference in mice

Three-month old, male Swiss Webster mice were born to either control dams or dams who had been prenatally stressed with light, heat, noise and handling during the last week of gestation. As adults, male offspring were tested on sexual partner preference and sexual behavior (mounting, intromissions and lordosis) with a sexually experienced male stimulus animal and a stimulus estrous female. In comparison to males born to control dams, prenatally stressed males showed a sexual partner preference for the sexually active male as demonstrated by a negative partner preference score, more and longer visits to the male's compartment, fewer and shorter visits to the female's compartment and longer latencies to and lower frequencies of mounts and intromissions of females. In addition, stressed males showed a greater frequency of lordosis and a higher lordosis quotient than did control males. This study is the first to investigate the effects of prenatal stress alone, without hormonal manipulation, on sexual partner preference using both a partner preference paradigm and measures of sexual behavior such as mounting, intromissions and lordosis. These findings support the suggestion that prenatal stress alone is enough to significantly affect sexual partner preference in male mice.     

The effects of cocaine on maternal behaviors in the rat.

Although recent research has focused on the behavioral teratology of cocaine, there has been little attention centered on the effects of cocaine use on parenting behaviors after birth. This experiment investigated the effects of cocaine on parental (generally termed maternal) behavior in the rat. Four types of adult rats were tested for these effects over a 10-day testing period: lactating primiparous female dams, primiparous females, nulliparous females, and males. Subjects were injected daily with cocaine (5 mg/kg) or saline. Ten minutes postinjection each subject was placed in a cage with three stimulus pups and nesting material, and observed for several measures of maternal behavior for 5 minutes, including sniffing, licking, and retrieving pups. Subjects were also rated on a maternal behavior scale at 60 minutes and 24 hours postinjection, and on nest quality. Cocaine reduced both the total number and duration of sniffing and licking maternal behaviors, and resulted in a lower maternal behavior rating at 60 minutes compared to saline-treated subjects. Among those subjects that retrieved pups within the first 5 minutes, cocaine-injected subjects retrieved for a longer duration. These results also suggest impaired maternal behavior, since rapid retrievals would have been more efficient in maintaining a nest huddle. Thus, cocaine impaired the parenting ability of both male and female rats, with and without previous parenting experience.     

Mouse pup urine as an infant signal

Drops of urine from donors of different ages and sexes were applied to the anogenital regions of 19-day fetuses, killed by freezing, that ordinarily are weak in stimulating parental care. These fetuses were then presented to virgin, naive albino mice (Mus musculus). In Experiment 1, fetuses treated with urine of 6-day-old pups were more stimulating than fetuses treated with water. Differences in contact, picking-up, retrieval, licking and self grooming were significant. The sex of the donor revealed no effect. In Experiment 2, urine from 10-day-old pups was found to be more effective than urine from 4-day-old pups, with different effects on contact and retrieval. Urine from pups was also more effective than urine from adults, because of different effects on contact, picking-up, retrieval, licking and nest building. The effects of urine from adult virgin females differed less from those of pup urine than did the effects of urine from adult males. Compared with the latter the adult female urine had different effects on picking-up, licking and cannibalism. Speculations are made about an infant factor that might be still active in the urine of adult females.     

Intra-uterine nutrition and its effects on aggression

Prenatal zinc deficiency and prenatal undernutrition were found to have adverse effects on the food consumption and weight gain of pregnant dams and their offspring. Pups whose dams suffered prenatal zinc deficiency (ZD) consumed less food and gained less weight than pups whose dams suffered prenatal undernutrition (PF). The PF pups consumed less food and gained less weight than pups whose dams were normally fed (AL). The ZD females at age 75 days were significantly more aggressive than the PF females, while the PF females were more aggressive than the AL females. At age 105 days, ZD females were significantly more aggressive than the PF and AL females. There were no differences in aggression between the PF and AL females at 105 days. Among the ZD, PF, and AL male offspring, there were no differences in aggression at either age level except that the 75 day old PF males were significantly less aggressive than the AL males. Thus prenatal malnutrition, especially zinc deficiency, seems to have differential effects on the aggressive tendencies of female and male offspring.     

Prenatal stress feminizes juvenile play patterns in male rats.

Sexually dimorphic rough-and-tumble play patterns were compared in male and female rats derived from control mothers and mothers stressed from days 14-21 of pregnancy. Animals were weaned into groups of 8 consisting of 2 males and 2 females from each treatment. Play in the home cage was recorded at 25, 28, 31, 34, 37 and 45 days of age and was most intense on day 31. The overall level of play was significantly higher in control males than in females or stressed males. Control males showed higher levels of the pinning component of rough-and-tumble play than females or stressed males. No play partner preferences were detected in any group. In adulthood, a higher percentage of stressed than control males displayed the female lordotic pattern. No deficits in ejaculatory behavior occurred in the stressed males. Since maternal stress alters patterns of plasma testosterone in male fetuses, the data suggest that the sexual differentiation of social play begins during prenatal ontogeny in the rat. The present results show that sexually dimorphic behaviors displayed before puberty are incompletely masculinized in prenatally stressed males, a finding similar to that reported for a number of adult behaviors.     

The influence of natural variations in maternal care on play fighting in the rat

Naturally occurring variations in maternal care in the rat influence the sensitivity of offspring to stress in adulthood. The offspring of mothers that show lower levels of pup licking/grooming (i.e., low-LG mothers) demonstrate enhanced responses to stress and increased anxiety compared to those of high-LG mothers. Low-LG offspring are also more sensitive to the influence of environmental enrichment than high-LG offspring. This study examined play fighting in the juvenile offspring of high-LG and low-LG dams in a multiple-play partners housing environment. Male offspring from low-LG dams demonstrated a significantly higher frequency of pouncing, pinning and aggressive social grooming than did high-LG males and high-LG and low-LG females. Consistent with earlier reports, male pups engaged in more play fighting than did females and maternal care was associated with differences in play fighting but only in males. Lower levels of stimulation in the form of LG from the dam during perinatal development may thus increase sensitivity for the stimulating effects of play behavior in periadolescence, in part explaining the increased solicitation of play fighting through increased pouncing in the male offspring of the low-LG mothers. These findings identify a possible influence of variations in maternal care on play fighting and suggest that maternal care in the perinatal period influence social interactions during periadolescence.     

Behavioral responses of infant rats to maternal licking: variations with age and sex

Behavioral interactions of Norway rat pups and their dams during maternal anogenital licking (AGL) were observed. Regularities in posture and orientation that may facilitate AGL were noted, and age-related changes in the pup's postural adjustments that may contribute to the decline of AGL in the 3rd postpartum week were described. It was found that cutaneous stimulation of the perineum, such as that provided by AGL, stimulates a characteristic leg extension response from pups. It was concluded that this response, which includes immobility and extension of all limbs, may permit maternal licking to continue long enough to stimulate the pup to eliminate and to allow the dam to ingest the urine. Males and females were found to exhibit similar responses and similar age-related changes. However, the latency from onset of AGL to performance of the leg extension response was shorter in males.     

Reductions in maternal food and water intake account for prenatal stress effects on neurobehavioral development in B6D2F2 mice

This study evaluated the role of stress-induced reductions in food intake in pregnant B6D2F1 mice in the production of developmental abnormalities in the offspring. One group of dams underwent one hour of physical restraint stress twice daily from days 12 to 17 of gestation. A second group was not restrained but, during this period, each dam was pair-fed to a weight-matched partner in the stressed group. A third group was left undisturbed and allowed unlimited access to lab chow and water. The restraint stress procedure reduced the average daily food and water intake in the dams, resulting in lower maternal weights, with the unstressed pair-fed group being affected more severely than the stressed group. The offspring of both the stressed and pair-fed dams were lighter than the offspring of the dams fed ad lib on day 20 postconception, and exhibited lower brain weights on day 32 postconception. Neurobehavioral development, as assessed on a battery of sensorimotor tests on day 32 postconception, was retarded in the prenatally stressed pups in comparison to the ad lib pups, while the pair-fed pups did not differ from either group. There were no differences among any of the groups on day 50 body or brain weight, body or tail length, anogenital distance, or locomotion, rearing and defecation in the open field.(ABSTRACT TRUNCATED AT 250 WORDS)     

Medial preoptic lesions disrupt parental behavior in both male and female California mice (Peromyscus californicus)

California mice (Peromyscus californicus) are monogamous and naturally biparental, making them an ideal species in which to study the neural basis of paternal behavior. A male or female from each male-female pair was given an electrolytic or sham lesion in the medial preoptic area (MPOA), an area known to be critical for the expression of maternal behavior in rats, and retested for parental responsiveness. MPOA-lesioned males and females showed significantly longer latencies to show parental behavior and spent significantly less time near pups, sniffing pups, and licking pups than sham-lesioned mice. However, MPOA lesions did not reduce time spent hovering over pups. The results suggest that the neural mechanisms mediating paternal behavior are similar to those mediating maternal behavior in this species.     

Effects of maternal care on the development, emotionality, and reproductive functions in male and female rats

Variations in maternal behavior induce long-lasting effects on behavioral and neuroendocrine responses to stress. The aim of this study was to analyze developmental parameters, reproductive function, and anxiety-related behaviors of male and female rats raised by mothers that naturally display high and low levels of maternal licking behavior. Results showed that an increase in licking behavior received by the pups accelerated their eye opening and reduced fear behavior assessed in the open field test. Additionally, female offspring of high licking (HL) mothers showed decreased ovulation and lordosis intensity. In contrast, males from HL and low licking (LL) mothers did not differ in their reproductive function, suggesting a gender difference in maternal effects. Present results showed that individual differences in maternal behavior appear not only to be predictive of later emotionality and stress-responsivity in the offspring, but can also modulate the reproductive function of females. Maternal genetic factors, differences in the prenatal intrauterine milieu, or a combination of these cannot be excluded to explain the effects observed.     

Pheromones and novel male-induced pregnancy disruptions in mice: exposure to conspecifics is necessary for urine alone to induce an effect

Previous research indicates a role of pheromones in novel male-induced early pregnancy disruptions. Although some reports suggest that urine alone is sufficient to produce this effect, others raise procedural concerns and fail to replicate such effects. On Days 1 to 5 after insemination, female CF-1 mice had their nasal regions repeatedly painted with water, urine from males housed in isolation, or urine from males housed in proximity to females. Almost all (87.5%) of the control females delivered litters. There was a small nonsignificant reduction in proportion parturient (78.5%) among females exposed to urine of males housed without social contact. The proportion of females parturient (57.1%) after treatment with urine from males housed in proximity to females was significantly different from controls. The magnitude of the effect of socially stimulated male urine is substantially less than that recorded when males are housed directly above inseminated females separated by a wire-mesh grid. These data suggest that production of pregnancy-disrupting male pheromones is stimulated by contact with conspecifics.     

Sexual motivation is demasculinized, but not feminized, in prenatally stressed male rats

Sexual motivation and copulation in male rats are associated with dopamine release in the nucleus accumbens. Demasculinized copulatory behavior has been demonstrated in prenatally stressed adult male rats. We have previously reported that approximately 80% of prenatally stressed male rats do not exhibit copulation and that no significant changes in nucleus accumbens dopamine release are seen during exposure to estrous females. In the present study, we investigated whether prenatal stress affects sexual motivation in these animals as adults. Pregnant Wistar rats were subjected to immobilization stress for two hours daily from day 15-19 of gestation. The prenatally stressed male offspring at the age of 3 months were allowed contact with receptive female rats for a 30 min period per week for 10 weeks; then, between the age of 5 and 6 months, their sexual motivation and copulatory activity were measured. Sexual motivation was measured in terms of sexual partner preference. The number of visits and the duration of each visit to an estrous female (stimulus female) or to a sexually active male rat (stimulus male) were recorded. Compared with control males, prenatally stressed male rats showed a significantly lower number of visits and a shorter duration of each visit to stimulus females. Prenatally stressed males showed no preference for male or female stimulus rats in terms of the number of visits and the duration of each visit, whereas control rats showed a significantly higher number of visits and duration of visits to female stimulus rats than male stimulus rats. A significant decrease in copulatory activity was observed in the prenatally stressed male offspring compared with control male rats, with most of the prenatally stressed males failing to show copulation. In vivo microdialysis experiments were performed on the nucleus accumbens with concurrent observation of sexual behavior. The prenatally stressed rats that did not exhibit copulation showed no significant changes in nucleus accumbens dopamine release during exposure to a stimulus male behind a wire-mesh barrier and the amount of dopamine release remained at the basal levels during actual physical contact. These results, combined with those of our previous report, indicate that sexual motivation in prenatally stressed male rats is demasculinized, but not feminized.     

Prenatal stress produces sex differences in nest odor preference

Prenatal stress (PS) and early postnatal environment may alter maternal care. Infant rats learn to identify their mother through the association between maternal care and familiar odors. Female Wistar rats were exposed to restraint stress for 30 min, 4 sessions per day, in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatal non-stressed mothers raising non-stressed pups (NS:NS), prenatal stressed mothers raising non-stressed pups (S:NS), prenatal non-stressed mothers raising stressed pups (NS:S), prenatal stressed mothers raising stressed pups (S:S). Maternal behaviors were assessed during 6 postpartum days. On postnatal day (PND) 7, the behavior of male and female pups was analyzed in the odor preference test; and noradrenaline (NA) activity in olfactory bulb (OB) was measured. The results showed that restraint stress increased plasma levels of corticosterone on gestational day 15. After parturition, PS reduced maternal care, decreasing licking the pups and increasing frequency outside the nest. Female pups from the NS:S, S:NS, S:S groups and male pups from the S:S group showed no nest odor preference. Thus, at day 7, female pups that were submitted to perinatal interventions showed more impairment in the nest odor preference test than male pups. No changes were detected in the NA activity in the OB. In conclusion, repeated restraint stress during the last week of gestation reduces maternal care and reduces preference for a familiar odor in rat pups in a sex-specific manner.