Dexamethasone can prevent stress-related litter deficits in the golden hamster

This study was designed to examine the effects of social subordination during early pregnancy in the golden hamster (Mesocricetus auratus). Primiparous females were mated to proven breeders and stressed during early pregnancy. Females were housed singly throughout gestation except for Days 4, 5, and 6 when they were paired for 10-min intervals three times each day with another female matched for age, weight, and day of pregnancy. Within each of the pairs, one female was consistently dominant to the other. Controls were exposed to a novel area instead of a conspecific. At parturition, all pups were counted, sexed, and weighed. There were no significant differences between control and dominant females' litter sizes and sex ratios. Subordinate females produced significantly smaller litters than control or dominant dams and significantly lower sex ratios than control dams. Subordinates produced fewer males than control or dominant dams, but there were no differences in the number of females produced. The entire experiment was repeated exactly except that females received a small dosage of dexamethasone in their drinking water on Days 3-7 of pregnancy. In this second group, there were no significant reductions in mean litter size, sex ratio, or pup weights among litters born to subordinate dams. These results suggest that subordinate dams produce smaller litters via selective resorption of males in utero and that the typical adrenal response to stress mediates this response.     

Simple disturbance of the dam in the neonatal period can alter haloperidol-induced catalepsy in the adult offspring

Three experiments were performed to determine whether apparently minimal disturbances of dams and litters would influence haloperidol-induced akinesia. In Experiment I, Long-Evans hooded rats (a) were left unmanipulated, (b) received nestcage relocation and observation, (c) received nestcage relocation/observation and maternal separation, or (d) received nestcage relocation/observation and pup handling. The male adult offspring received open-field testing and later received forepaw-on-dowel catalepsy testing following saline, morphine (20 mg/kg), or haloperidol (2 mg/kg). In Experiment II, hooded rats received (a) no manipulation, (b) nestcage relocation, (c) maternal separation, or (d) pup handling. At weaning, dams were tested in the open-field. Activity wheel locomotion of the offspring was assessed following saline or haloperidol for 3 days/week for 3 weeks; then, 5 and 7 days later, rats received haloperidol (0.5 mg/kg) and catalepsy testing. In both experiments, manipulations involving the dam reduced the offsprings' haloperidol-induced catalepsy, but, in Experiment II, a history of haloperidol administration distinguished between the effects of nestcage relocation and maternal separation. In Experiment III, Swiss albino mice received (a) no treatment, (b) nestcage relocation and maternal separation, (c) relocation/separation and mild cold stress of pups, (d) relocation/separation and pup handling, or (e) relocation/separation and severe cold stress of pups. Adult male mice received saline or haloperidol (2.5 mg/kg) and inclined grid catalepsy testing. Mice receiving relocation/separation and mice receiving relocation/separation and severe cold stress showed enhanced catalepsy versus control mice. Thus, it was concluded that seemingly innocuous events in infancy can influence the intensity of extrapyramidal side effects of neuroleptics in adulthood.     

Vasopressin, maternal behavior, and pup well-being

The brain peptide, vasopressin (VP), was studied with respect to its effects on maternal care in rearing natural and cross-fostered pups. Long-Evans (LE) rats synthesize hypothalamic VP; whereas, Brattleboro (DI) rats do not produce this peptide. Long-Evans dams exhibited superior maternal care when compared with DI dams when rearing their own as well as foster pups. This enhanced behavior was evidenced by the higher survival rate of pups reared by LE mothers compared to those reared by DI mothers. Later, when the offspring were subjected to the stress of 23 hours of food restriction each day, LE animals reared by their natural mothers survived for a significantly longer period of time and developed significantly less stomach pathology than DI animals reared by their natural mothers or LE foster mothers. The results demonstrated that the secondary factor of maternal care in the absence of VP was of little consequence in the characteristic difficulties observed in DI offspring.     

Vasopressin,maternal behavior,and pup well-being

The brain peptide, vasopressin (VP), was studied with respect to its effects on maternal care in rearing natural and cross-fostered pups. Long-Evans (LE) rats synthesize hypothalamic VP; whereas, Brattleboro (DI) rats do not produce this peptide. Long-Evans dams exhibited superior maternal care when compared with DI dams when rearing their own as well as foster pups. This enhanced behavior was evidenced by the higher survival rate of pups reared by LE mothers compared to those reared by DI mothers. Later, when the offspring were subjected to the stress of 23 hours of food restriction each day, LE animals reared by their natural mothers survived for a significantly longer period of time and developed significantly less stomach pathology than DI animals reared by their natural mothers or LE foster mothers. The results demonstrated that the secondary factor of maternal care in the absence of VP was of little consequence in the characteristic difficulties observed in DI offspring.     

Oxytocin links mothering received,mothering bestowed and adult stress responses

We review recent discoveries that implicate oxytocin in the intergenerational transmission of similar levels of maternal behavior and acute stress responses in female rats. First, ICV-infused oxytocin antagonist decreased the display by nursing dams of pup-licking (PL) and arched-back nursing (ABN), but not other components of maternal behavior, and increased maternal self-grooming suggesting that oxytocin may shift the balance of oral grooming by dams away from themselves and toward pups. Second, oxytocin receptor concentrations in areas of the adult brain where oxytocin stimulates maternal behavior or diminishes anxiety and adrenal axis responses to acute stress were positively related to PL-ABN received during infancy. Third, oxytocin and oxytocin antagonist treatments of pups on postnatal days 2-10, respectively increased and decreased PL by the treated rats when adult and themselves nursing dams. This indicates that oxytocin activity in female pups, which may be regulated by PL-ABN received from their mothers, influences their adult levels of PL. These three lines of evidence suggest that oxytocin selectively enhances PL-ABN by rat dams, which then increases oxytocin activity in female pups and, thereby, facilitates their expression of central oxytocin receptors (and perhaps other aspects of central oxytocin systems) and, consequently, their adult PL-ABN frequencies and acute stress responses.     

Maternal behavior of spontaneously hypertensive and Wistar-Kyoto normotensive rats: effects of reciprocal cross-fostering of litters

Maternal behavior of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive dams rearing either their natural pups or pups of the opposite strain was assessed when pups were 4-6 days of age. Consistent with previous reports, SHR dams caring for their natural pups were observed nursing and licking their pups more often than WKY dams and were away from their pups less often. The behavior of dams rearing cross-fostered pups demonstrated that this strain difference in patterns of maternal behavior is dependent on pup type. Mothers of both strains shifted their behavior in the direction of the opposite strain's maternal behavior pattern when caring for cross-fostered pups. This shift was most pronounced in SHR dams caring for WKY pups. These data suggest that alterations in patterns of maternal behavior produced by cross-fostering may play an important role in cross-fostering effects on the physiological development of SHRs previously reported.     

Effects of serotonergic and cholinergic antagonists on suckling behavior of neonatal, infant, and weanling rat pups

In Experiment 1, Sprague-Dawley rat pups at postnatal days 3-4, 7-8, 10-11, 15-16, and 23-24 were tested for suckling behavior on their anesthesized multiparous dams following administration of metergoline or scopolamine. The serotonergic antagonist, metergoline, inhibited suckling in 3- to 4- and 7- to 8-day-old rat pups, but was not found to influence suckling in older pups. Scopolamine, a cholinergic antagonist, reduced suckling primarily in 3- to 4-day-old pups. In Experiment 2, parity of the maternal female was manipulated to assess whether this variable would influence suckling behavior and the effects of metergoline on suckling of weanlings. Baseline levels of suckling were reduced in 23- to 24-day-old pups of primiparous dams when compared with multiparous-derived offspring. Administration of metergoline increased the amount of time that these primiparous-derived pups spent attached to nipples, but did not influence suckling of offspring of multiparous dams, perhaps as a result of a ceiling effect on suckling behavior in these animals.     

Effect of conspecific sex on aggression during pregnancy and lactation in golden hamsters

The effect of conspecific sex on maternal aggression in hamsters was determined by comparing the frequency of aggressive responses by dams continuously housed with either a virgin male or female cagemate during pregnancy and lactation. Dams easily established aggressive dominance over male cagemates soon after pairing, and their aggression was low thereafter for the duration of pregnancy and lactation. The aggression of dams with females, on the other hand, tended to fluctuate with highs during mid pregnancy and mid lactation and lows around birth. When dam aggression was low around birth, female cagemates frequently became aggressively dominant, and several dams lost their litters. The higher aggression of dams toward females than males is probably a reflection of greater intrasexual competition for environmental resources that includes pups.     

Immune stress in late pregnant rats decreases length of gestation and fecundity, and alters later cognitive and affective behaviour of surviving pre-adolescent offspring

Immune challenge during pregnancy is associated with preterm birth and poor perinatal development. The mechanisms of these effects are not known. 5α-Pregnan-3α-ol-20-one (3α,5α-THP), the neuroactive metabolite of progesterone, is critical for neurodevelopment and stress responses, and can influence cognition and affective behaviours. To develop an immune challenge model of preterm birth, pregnant Long-Evans rat dams were administered lipopolysaccharide [LPS; 30?μg/kg/ml, intraperitoneal (IP)], interleukin-1β (IL-1β; 1?μg/rat, IP) or vehicle (0.9% saline, IP) daily on gestational days 17-21. Compared to control treatment, prenatal LPS or IL-1β reduced gestational length and the number of viable pups born. At 28-30 days of age, male and female offspring of mothers exposed to prenatal IL-1β had reduced cognitive performance in the object recognition task compared to controls. In females, but not males, prenatal IL-1β reduced anxiety-like behaviour, indicated by entries to the centre of an open field. In the hippocampus, progesterone turnover to its 5α-reduced metabolites was lower in prenatally exposed IL-1β female, but not in male offspring. IL-1β-exposed males and females had reduced oestradiol content in hippocampus, medial prefrontal cortex and diencephalon compared to controls. Thus, immune stress during late pregnancy reduced gestational length and negatively impacted birth outcomes, hippocampal function and central neurosteroid formation in the offspring.     

Effects of chronic social stress during lactation on maternal behavior and growth in rats

Maternal mood disorders such as depression and chronic anxiety can negatively affect the lives of not only mothers, but also of partners, offspring, and future generations. Chronic exposure to psychosocial stress is common in postpartum mothers, and one of the strongest predictors of postpartum depression is social conflict. The objective of the current study was to evaluate the effects of chronic social stress (CSS) during lactation on the maternal behavior (which consists of maternal care and aggression toward a novel conspecific) of lactating rats, as well as on the growth of the dams and their offspring. It was hypothesized that chronic daily exposure to a novel male intruder would alter the display of maternal behavior and impair growth in both the dam and offspring during lactation due to the potentially disruptive effects on maternal behavior and/or lactation. The data indicate that CSS during lactation attenuates maternal care and the growth of both dams and pups, and increases self-grooming and maternal aggression toward a novel male intruder. These results support the use of CSS as a relevant model for disorders that impair maternal behavior and attenuate growth of the offspring, such as postpartum depression and anxiety.     

Litter gender composition affects maternal behavior of the primiparous mouse dam (Mus musculus)

Thirty-nine litters of the outbred Swiss CD-1 mouse strain were reduced at birth to 6 pups, according to three conditions: MM (all males), MF (3 males and 3 females), or FF (all females). The maternal behavior of their respective dams (frequency and duration of nursing, licking, nest-building, and other activities such as eating, drinking, sniffing, grooming, and undirected locomotor activity) were scored during a single 10-min session on Days 2, 3, 5, 7, 10, 14, and 18. Dams rearing MM litters showed higher scores of maternal care on Days 2 and 18 in the case of nursing, on Days 2, 7, and 10 in the case of nest-building, and on Day 18 in the case of licking. These results confirm previous rat data, which indicated that male and female pups are exposed early in infancy to a different pattern of maternal behavior. Concomitant measurements of pup development (body-weight gain and achievement of a number of physiological and neurobehavioral landmarks) indicated that these effects of litter gender composition are not mediated by gross changes in the maturational trends of the pups.     

The role of the accessory and main olfactory systems in maternal behavior of the primiparous rat

The objective of this study was to analyze the respective roles of the main and accessory olfactory systems in the development of maternal behavior in the primiparous Wistar rat. Females underwent one of the following treatments: vomeronasal nerve section (VN), irrigation of nasal cavities with 5% ZnSO4 solution (ZN), surgical control, saline irrigation control, and normal control. Surgical or first irrigation were done before mating occurred. Irrigations were done every 7 days thereafter. The dams and their litters were observed from the day the litter was born (Day 1) through Day 16. Pup weights and temperatures were recorded daily. Home cages were checked daily for changes in nest location and number of times pups were found out of the nest. Retrieving tests were conducted on Days 4, 7, 10, and 13. The following behavioral items were observed: number of pup retrievals , number of times mother nosed or licked pups, percentage of litter returned to nest by end of test, dam self-grooming, dam climbing or rising, and dam digging or burrowing in shavings. The VN dams and their litters were not significantly different from the control dams and their litters on any of the measures taken. The ZN dams and their litters were not significantly different from their controls on all measures except for pup body temperature which was slightly lower from Day 13 through day 16 and pup body weight which was slightly lower from Day 12 through Day 16. Since these differences are very small, they do not seem to indicate a serious deficiency in maternal behavior. The results indicate that adequate maternal behavior develops with either of the two systems intact.     

Hysterectomy-induced maternal behavior during pregnancy in the rat.

Hysterectomies were performed between the 10th and 19th day of pregnancy, and females were tested with pups for the onset of maternal behavior starting 0,24, 48, or 72 hr after surgery. Pups remained with the females overnight, and testing was repeated daily with fresh pups until females exhibited maternal behavior. Latencies for the onset of maternal behavior were shorter after hysterectomy on the 10th and 16th days of pregnancy than in intact pregnant females at the same stages of pregnancy; latencies became shorter, the later the termination of pregnancy. When the ovaries were removed along with hysterectomy during pregnancy, short-latency maternal behavior no longer was exhibited. Pregnant females were tested during the last 40 hr of pregnancy: nest building began at 34 hr prepartum and retrieving at 28 hr prepartum. The effect of hysterectomy during pregnancy on ovarian secretion of estrogen and progesterone is reviewed, and it is concluded that the rise in estrogen secretion, which follows hysterectomy during pregnancy, is most likely the cause of the rapid onset of maternal behavior after hysterectomy. A similar proposal is made for the prepartum onset of maternal behavior in intact pregnant females.     

Housing pregnant mice (Mus musculus) in small groups facilitates the development of odor-based homing in offspring

Infant mice (Mus musculus) born to dams housed in isolation throughout pregnancy (IsoPreg) begin differentially approaching homenest bedding over clean bedding on Postnatal Day 6. Offspring of dams housed with 2 other potentially pregnant conspecifics (SocPreg) display such homing behavior on Day 4. Earlier onset of homing reflects facilitated olfactory responsiveness in SocPreg pups, rather than qualitative or quantitative differences in IsoPreg versus SocPreg nest odors, body growth, or motoric capabilities. Exposing pregnant IsoPreg dams to SocPreg bedding also accelerated homing onset in the offspring, though not to the same extent as the full social context. Thus, it appears that the facilitation of homing is mediated through the pregnant dam by a combination of chemical cues and other social stimuli.     

Rat gestation during space flight: Outcomes for dams and their offspring born after return to earth

Sprague-Dawley rats were studied to learn whether gestation in the near-zero gravity, high radiation environment of space impacts selected mammalian postnatal events. Ten rats spent days nine to twenty of pregnancy aboard the space shuttle orbiterAtlantis (STS-66). Their movement, was studied shortly after return to Earth; subsequently, several of their offspring were cross-fostered and examined through postnatal day 81 (P81) for whole body growth and somatic motor development. Values for the flight animals were compared to ground-based control groups. Relative to controls, the pregnant flight rats showed a marked paucity of locomotion during the first few hours after returning to Earth. There was greater likelihood of perinatal morbidity for the offspring of flight dams when compared to the control groups. Whole body weight of surviving offspring, averaged for each group separately, showed typical sigmoidal growth curves when plotted against postnatal age. The flight group for our study had a larger ratio of female to male pups, and that was sufficient to account for the lower average daily weight gained by the flight animals when compared to the control groups. Walking was universally achieved by P13 and preceded eye opening which was complete in all pups by P17. Thus, both of these developmental horizons were attained on schedule in the flight as well as the control rats. Characteristic changes were observed in hind limb step length and gait width as the pups grew. These patterns occurred at the same time in each group of rats. Therefore, prenatal space flight from days nine to twenty of gestation did not interfere with the establishment of normal patterns for hind paw placement during walking.     

Maternal supplementation of nucleotides improves the behavioral development of prenatal ethanol-exposed mice

Maternal ethanol consumption during pregnancy can induce learning deficits in the offspring. The objective of this study was to assess whether supplementation of exogenous nucleotides during pregnancy and lactation would ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, and to explore the possible mechanisms. In the present study, pregnant C57BL/6J mice were exposed to ethanol (5 g/kg body weight) intragastrically from gestational day (GD) 6 to GD15. The dams in exogenous nucleotide intervention groups were fed with feed containing 0.01 %, 0.04 %, or 0.16 % nucleotide powder, with control and ethanol groups receiving normal feed. The dams were allowed to deliver naturally and to breast feed their offspring. After weaning, behavioral tests were carried out in the offspring of each group. Serum oxidation indexes were analyzed, and the hippocampus of each offspring was collected and detected for acetyl cholinesterase (AChE) activity and the expression of p-CREB, CREB, and BDNF. The results showed that maternal supplementation with exogenous nucleotides during pregnancy could ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, through improving their antioxidant capacity, reversing hippocampus AChE levels, and allowing the expression of some proteins related to learning and memory. However, different sensitivities were found between the two sexes.     

Milk availability modulates weaning in the Norway rat (Rattus norvegicus)

Two experiments were conducted to investigate the role of milk availability in the development of independent feeding and drinking in the Norway rat pup. Beginning on Day 14 postnatally, pups were exposed to different levels of milk supply by changing litter size from 8 to 4 versus 12 pups (Experiment 1) or limiting temporally the pups' access to a lactating dam to 8, 14, or 24 hr daily (Experiment 2). Both manipulations accelerated weaning in milk-poor pups in comparison with same-age pups with relatively greater milk supplies. By adding solid food and water to their diet, early weaning pups compensated for the negative energy consequences of milk reduction and achieved premanipulation growth rates. Milk availability thus appears to affect weaning, and it is suggested that the developmental changes in the nutritive energy balance between mother and offspring contribute to the emergence of independent ingestion.     

The effects of prenatal maternal stress on children's cognitive development: Project Ice Storm

There exists considerable research on the effects of prenatal maternal stress on offspring. Animal studies, using random assignment to experimental and control groups, demonstrate the noxious effects of prenatal maternal stress on physical, behavioural and cognitive development. The generalizability of these results to humans is problematic given that cognitive attributions moderate reactions to stressors. In humans, researchers have relied upon maternal anxiety or exposure to life events as proxies for the stressors used with animals. Yet, the associations between maternal anxiety or potentially non-independent life events and problems in infants are confounded by genetic transmission of temperament from mother to child. We summarize the literature on prenatal maternal stress and infant cognitive development, leading to the conclusion that the human literature lacks the ability to separate the effects of the objective exposure to a stressor and the mother's subjective reaction. We then describe our prospective Project Ice Storm in which we are following 150 children who were exposed in utero to a natural disaster. We demonstrate significant effects of the objective severity of exposure on cognitive and language development at age two years with important moderating effects of the timing during pregnancy. The implications of our findings are discussed.     

Infanticide and maternal aggression: Synchrony of male and female reproductive strategies in mice

Thirty-six percent of male mice from three strains attacked newborn pups sired by another male. No male attacked its own offspring. Females did not show differential aggression toward males likely (strangers) or unlikely (sires) to attack their pups. Both forms of aggression were unaffected by housing in rooms which did or did not contain the aggression targets. The three strains differed in strength of maternal aggression but not in the incidence of infanticide. Females showed more aggression when mated with males of the same, rather than a different, strain but no differences with intruders of the same or a different strain. Infanticide by males is best viewed as a postcopulatory, intermale-competition strategy, and maternal aggression as a counter strategy.     

Effects of daily and acute restraint stress during lactation on maternal aggression and behavior in mice

A decreased reactivity to stressors during lactation might heighten the expression of maternal care (including defense of offspring) by minimizing the extent to which stress can impact maternal care. Although stressors applied during pregnancy have variable effects on maternal aggression (or defense of offspring), to date no study has examined the effects of stress applied during the postpartum period on maternal aggression. In this study, we examined the effects of both daily and acute restraint stress (30 min) applied postpartum on maternal aggression and other maternal behaviors. Daily restraint (ending 2 h before testing) did not alter any measure of maternal behavior, including nursing, licking and grooming of pups and pup retrieval, or any measure of maternal aggression. In contrast, acute stress significantly impaired total time aggressive and number of attacks, but pup retrieval was normal. c-Fos levels were significantly elevated in a number of brain regions in association with acute stress, including lateral septum (LS), caudal periaqueductal gray and medial amygdala (MeA), suggesting possible sites where stress reactivity could alter aggression. Together, the results indicate that acute restraint stress impairs maternal aggression and provide a starting point for future studies examining how stress reactivity pathways may intersect with maternal aggression pathways.