Alterations In Maternal Behavior Research Articles

Altered Patterns of Maternal Behavior Transitions in Rats Exposed to Limited Bedding and Nesting Material Paradigm.

Maternal care plays a fundamental role in early life, and the alteration of its patterns can negatively affect the developmental course of the offspring in a myriad of domains in both rats and humans. The limited bedding and nesting (LBN) protocol is an extensively used paradigm in rodents to address the impact of altered maternal behavior patterns on infants' neurodevelopment. Here, we explore the altered patterns of maternal care in rats in LBN conditions by describing sequences of transition between maternal behavior components using network analysis. Using this technique, we capture how often maternal behavior transitions take place during the LBN period and which behaviors play central roles in those transitions over time. Female rats and their pups were placed in standard and LBN housing conditions from Postpartum Days 2 to 9, during which maternal behavior was observed during the light and dark phases. We used inferential statistical analysis to compare the maternal behavior profiles of control and LBN dams, and network analysis was used to capture the altered sequence of maternal behavior transitions during the period of LBN. Compared to control dams, LBN dams significantly increased their high crouch nursing posture during light/dark phases (p=0.018), and the number of behavioral transitions increased only during the dark phase (p=0.0004). Network analysis revealed specific altered patterns of behavioral transitions in LBN dams, characterized by the predominance of switches between active nursing postures during the first five days of the LBN protocol. Nursing behavior was the most disrupted component of maternal behavior under the LBN protocol, mainly during the dark phase. Network analysis can complement and extend traditional methods to gain a more thorough understanding of maternal care strategies and behavioral patterns in LBN conditions and potential consequences for the offspring.

Protein-caloric restriction induced HPA axis activation and altered the milk composition imprint metabolism of weaned rat offspring

ObjectivesMaternal protein-caloric restriction during lactation can malprogram offspring into having a lean phenotype associated with metabolic dysfunction in early life and adulthood. The aim of this study was to investigate the relationships between nutritional stress, maternal behavior and metabolism, milk composition, and offspring parameters. Additionally, we focused on the role of hypothalamus–pituitary–adrenal axis hyperactivation during lactation. MethodsDams were fed a low-protein diet (4% protein) during the first 2 wk of lactation or a normal-protein diet (20% protein) during all lactation. Analyses of dams, milk, and offspring were conducted on postnatal days (PD) 7, 14, and 21. ResultsBody weight and food intake decreased in dams, which was associated with reduced fat pad stores and increased corticosterone levels at PD 14. The stressed low-protein diet dams demonstrated alterations in behavior and offspring care. Despite nutritional deprivation, dams adapted their metabolism to provide adequate energy supply through milk; however, we demonstrated elevated corticosterone and total fat levels in milk at PD 14. Male offspring also showed increased corticosterone at PD 7, associated with a lean phenotype and alterations in white and brown adipose tissue morphology at PD 21. ConclusionExposure to protein-caloric restriction diet of dams during lactation increased the glucocorticoid levels in dams, milk, and offspring, which is associated with alterations in maternal behavior and milk composition. Thus, glucocorticoids and milk composition may play an important role in metabolic programming induced by maternal undernutrition.

Exposure to environmentally relevant doses of plasticizers alters maternal behavior and related neuroendocrine processes in primiparous and multiparous female mice

Phthalates are organic pollutants frequently detected in the environment. The effects of these substances on male reproduction have been extensively studied but their potential impact on female reproductive behaviors in particular at environmental doses still remains to be documented. In the present study, we examined the effects of chronic exposure to di (2-ethylhexyl) phthalate (DEHP) alone at 5 or 50 μg/kg/d, or in an environmental phthalate mixture on maternal behavior of lactating female mice after a first (primiparous) and a second gestation (multiparous). Exposure of DEHP alone or in a phthalate mixture reduced pup-directed behaviors, increased self-care and forced nursing behaviors and altered nest quality for both primiparous and multiparous dams. In pup-retrieval test, primiparous and multiparous dams exposed to DEHP alone or in a phthalate mixture retrieved their pups more rapidly, probably due to a higher emission of ultrasonic vocalizations by the pups. At lactational day 2 following the third and last gestational period, the neural circuitry of maternal behavior was analyzed. A lower number of oxytocin-immunoreactive neurons in the paraventricular and anterior commissural nuclei was found in dams exposed to DEHP alone or in a phthalate mixture, while no changes were observed in the number of arginine-vasopressin immunoreactive cells. In the medial preoptic area, exposure to DEHP alone or in a phthalate mixture reduced ERα-immunoreactive cell number. Dendritic spine density assessed for DEHP at 5 μg/kg/d was also reduced. Thus, exposure to DEHP alone or in a phthalate mixture altered maternal behavior probably through a neuroendocrine mode of action involving oxytocin and estrogen through ERα, key pathways necessary for neuroplasticity and behavioral processing.

Sex- and age- dependent effect of pre-gestational chronic stress and mirtazapine treatment on neurobehavioral development of Wistar rat offspring.

Hormonal fluctuations, such as the perinatal period, may increase susceptibility of women to depression, which in turn exert a negative impact on child’s neurodevelopment, becoming a risk factor in development of neuropsychiatric disorders. Moreover, the use of antidepressants during this critical period presents a serious health concern for both the mother and the child, due to the consequences of treatment in terms of the reliability and safety for the proper neurodevelopment of the organism being not well known. Atypical antidepressants, such as mirtazapine, that targets both serotonergic and noradrenergic systems in the central nervous system (CNS), represent a novel focus of research due to its unique pharmacological profile. The aim of this work was to study the effects of maternal depression and/or perinatal antidepressant mirtazapine treatment on the neurobehavioral development of the offspring. Pre-gestationally chronically stressed or non-stressed Wistar rat dams were treated with either mirtazapine (10 mg/kg/day) or vehicle during pregnancy and lactation followed by analysis of offspring’s behavior at juvenile and adolescent age. We found mirtazapine induced significant alterations of nursing behavior. In offspring, pregestational stress (PS) had an anxiogenic effect on adolescent males (p≤0.05) and increased their active behavior in forced swim test (p≤0.01). Interaction between pregestational stress and mirtazapine treatment variously induced anxiolytic changes of juvenile (p≤0.05) and adolescent (p≤0.05) females and impairment of spatial memory (p≤0.01) in adolescent females as well. Hippocampal density of synaptophysin, pre-synaptic protein marker, was decreased mainly by mirtazapine treatment. In conclusion, our results show mirtazapine induced significant alterations in maternal behavior and several sex- and age-dependent changes in neurobehavioral development of offspring caused by both prenatal mirtazapine treatment and/or chronic pregestational stress.

Effects of snack intake during pregnancy and lactation on reproductive outcome in mild hyperglycemic rats

Metabolic disorders, like diabetes, as well as maternal diet, alter nutrient availability in utero, inducing adaptations in the offspring. Whether the effects of maternal hyperglycemia are modulated by diet, however, has yet to be explored. In the current study, we examined this issue by giving females rats, treated neonatally with STZ to induce mild hyperglycemia, and control littermates either ad libitum access to standard chow (Control n = 17; STZ n = 16) or standard chow and snacks (Control-snack n = 18; STZ-snack n = 19) (potato chips and a red fruit-flavored sucrose syrup solution 1.5%) throughout pregnancy and lactation. We hypothesized that the maternal glucose intolerance typically seen in female rats treated neonatally with STZ would be exacerbated by snack intake, and that the combination of snack intake and STZ treatment would lead to alterations in maternal behavior and offspring development. Maternal body weight and food intake were measured daily through pregnancy and lactation and litter weight throughout lactation. At birth, litter size, offspring weight, body length, and anogenital distance were obtained and offspring were classified according to their weight. Measures of nursing and retrieval behavior, as well as exploration in the open field and the elevated plus-maze were also recorded. As predicted, snack intake tended to aggravate the glucose intolerance of STZ-treated rats during pregnancy. Both Control and STZ-treated females that had access to snacks ate more calories and fat, but less carbohydrate and protein than females having access to chow alone. Overall, STZ-treated dams gave birth to fewer pups. Chow-fed STZ females gave birth to a greater proportion of large for pregnancy age pups, whereas dams in the Control-snack group gave birth to a greater proportion of small pups. The birth weight classification of pups born to STZ-snack rats, however, resembled that of the Control chow-fed females. Although all litters gained weight during lactation, litters from snack-fed dams gained less weight regardless of maternal hyperglycemia and did not show catch-up growth by weaning. Overall, STZ rats spent more time nest building, whereas the average inter milk ejection interval was higher in snack-fed females. STZ-snack dams retrieved the complete litter faster than dams in the other groups. Together, these data suggest that when mild hyperglycemic females are given access to snacks throughout pregnancy and lactation their intake is similar to that of Control females given snack access. The combination of hyperglycemia and snack access tended to decrease glucose tolerance in pregnancy, and normalized birth weight classification, but produced few other effects that were not seen as a function of snack intake or hyperglycemia alone. Since birth weight is a strong predictor of health issues, future studies will further investigate offspring behavioral and metabolic outcomes later in life.

Maternal behavior and the neonatal HPA axis in the Wistar Audiogenic Rat (WAR) strain: Early-life implications for a genetic animal model in epilepsy

Epileptogenesis is a multistage process and seizure susceptibility can be influenced by stress early in life. Wistar Audiogenic Rat (WAR) strain is an interesting model to study the association between stress and epilepsy, since it is naturally susceptible to seizures and present changes in the hypothalamus–pituitary–adrenal (HPA) axis activity. All these features are related to the pathogenic mechanisms usually associated with psychiatric comorbidities present in epilepsy. Therefore, the current study aimed to evaluate the neonate HPA axis function and maternal care under control and stress conditions in the WAR strain. Maternal behavior and neonate HPA axis were evaluated in Wistar and WAR strains under rest and after the presence of stressors. We observed that WAR pups present higher plasmatic corticosterone concentration as compared to Wistar pups. Although WAR dams do not show significant altered maternal behavior at rest, there is a higher latency to recover the litter in the pup retrieval test, while some did not recover all the litter. Wistar Audiogenic Rat dams presented similar behaviors to Wistar dams to a female intruder and maternal care with the pups in the maternal defense test. Taken together, these findings indicate that the WAR strain could show HPA axis disruption early in life and dams present altered maternal behavior under stressful events. Those alterations make the WAR strain an interesting model to evaluate vulnerability to epilepsy and its associated neuropsychiatric comorbidities.

Corticotropin-releasing factor infusion in the bed nucleus of the stria terminalis of lactating mice alters maternal care and induces behavioural phenotypes in offspring

The peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated in anxiety behaviour and regulation of the stress response. The effects of intra-BNST CRF administration were compared with those induced by the limited bedding (LB) procedure, a model that produces altered maternal behaviour. BALB/cJ dams were exposed to five infusions of CRF or saline into the BNST in the first weeks after birth while the LB dams were exposed to limited nesting material from postnatal days (P) 2–9. Maternal behaviour was recorded in intercalated days, from P1-9. Offspring anxiety-like behaviour was assessed during adulthood using the open-field, elevated plus-maze, and light/dark tests. Both intra-BNST CRF and LB exposure produced altered maternal care, represented by decreased arched-back nursing and increased frequency of exits from the nest. These changes in maternal care resulted in robust sex-based differences in the offspring’s behavioural responses during adulthood. Females raised by CRF-infused dams exhibited increased anxiety-like behaviour, whereas males presented a significant decrease in anxiety. On the other hand, both males and females raised by dams exposed to LB showed higher locomotor activity. Our study demonstrates that maternal care is impaired by intra-BNST CRF administrations, and these maladaptations are similar to exposure to adverse early environments. These procedures, however, produce distinct phenotypes in mice during young adulthood and suggest sex-based differences in the susceptibility to poor maternal care.

Influence of gestational exercise practice and litter size reduction on maternal care

Mother-pup interactions are extremely important to offspring survival and growth. The goal of this study was to evaluate the influence of prenatal and neonatal interventions on maternal care, analyzing the effect of maternal exercise, as a healthy intervention, and also the litter size reduction, a model that has been widely used to study early overfeeding in rats. Female Wistar rats were divided into 1) sedentary, and 2) swimming exercise for four weeks, starting one week before mating (5 days/week, 30 min/session). One day after birth, the litter was culled to 8 pups (normal) or 3 pups (small) per dam, yielding control and overfed subgroups for each maternal group, respectively. From postnatal days 2–9 the litter was observed 5 periods a day, to evaluate maternal behavior. Litter reduction caused important alterations in maternal behavior, reducing the total time out of the nest and increasing the frequency of maternal care and lactation in several observation periods, justifying the increased pup’s weight gain already demonstrated by this animal model. The practice of maternal exercise did not prevent, but cause the less intensive frequency of non-maternal behavior and lactation in arched-back position, induced by the reduction of litter size. These data demonstrated that small litter size altered maternal behavior, and gestational exercise does not influence significantly these changes.

Lineage- and Sex-Dependent Behavioral and Biochemical Transgenerational Consequences of Developmental Exposure to Lead, Prenatal Stress, and Combined Lead and Prenatal Stress in Mice.

Background:Lead (Pb) exposure and prenatal stress (PS) during development are co-occurring risk factors with shared biological substrates. PS has been associated with transgenerational passage of altered behavioral phenotypes, whereas the transgenerational behavioral or biochemical consequences of Pb exposure, and modification of any such effects by PS, is unknown.Objectives:The present study sought to determine whether Pb, PS, or combined Pb and PS exposures produced adverse transgenerational consequences on brain and behavior.Methods:Maternal Pb and PS exposures were carried out in F0 mice. Outside breeders were used at each subsequent breeding, producing four F1-F2 lineages: [F1 female-F2 female (FF), FM (male), MF, and MM]. F3 offspring were generated from each of these lineages and examined for outcomes previously found to be altered by Pb, PS, or combined Pb and PS in F1 offspring: behavioral performance [fixed-interval (FI) schedule of food reward, locomotor activity, and anxiety-like behavior], dopamine function [striatal expression of tyrosine hydroxylase (Th)], glucocorticoid receptor (GR) and plasma corticosterone, as well as brain-derived neurotrophic factor (BDNF) and total percent DNA methylation of Th and Bdnf genes in the frontal cortex and hippocampus.Results:Maternal F0 Pb exposure produced runting in F3 offspring. Considered across lineages, F3 females exhibited Pb-related alterations in behavior, striatal BDNF levels, frontal cortical Th total percentage DNA methylation levels and serum corticosterone levels, whereas F3 males showed Pb- and PS-related alterations in behavior and total percent DNA methylation of hippocampal Bdnf. However, numerous lineage-specific effects were observed, most of greater magnitude than those observed across lineages, with outcomes differing by F3 sex.Discussion:These findings support the possibility that exposures of previous generations to Pb or PS may influence the brain and behavior of future generations. Observed changes were sex-dependent, with F3 females showing multiple changes through Pb-exposed lineages. Lineage effects may occur through maternal responses to pregnancy, altered maternal behavior, epigenetic modifications, or a combination of mechanisms, but they have significant public health ramifications regardless of mechanism. https://doi.org/10.1289/EHP4977

Preconception maternal cocaine self-administration increases the reinforcing efficacy of cocaine in male offspring.

Although the influence of gestational cocaine exposure on offspring has been the focus of a sustained research effort, the effect of preconception cocaine self-administration by dams on progeny has received far less attention. In the current study, adult female rats were allowed to self-administer cocaine 2h a day for 60days and then after a 10-day wash out period, bred to naïve males. Maternal behavior was measured in dams until weaning. When male and female progeny reached adulthood, anxiety-like behavior, memory, and cocaine self-administration were assessed in separate cohorts of rats. Despite a total of at least 30days of cocaine abstinence, the quality of maternal behaviors was negatively affected by previous cocaine exposure as reflected by less time spent with pups as well as an excess of other maladaptive maternal behaviors. Measures of anxiety-like behavior and memory were not affected by maternal cocaine intake in either male or female offspring. In contrast, male, but not female, the progeny of dams exposed to cocaine showed increased reinforcing efficacy of cocaine as measured by cocaine self-administration under a progressive ratio schedule. The fact that cocaine self-administration was influenced only in the male offspring of cocaine-exposed dams argues against this phenotype being linked to altered maternal behavior, although this possibility cannot be ruled out completely. Collectively, these results indicate that preconception cocaine self-administration by dams results in the relatively selective enhancement of cocaine addiction-like behavior in male offspring.

Cross-Generational Transmission of Early Life Stress Effects on HPA Regulators and Bdnf Are Mediated by Sex, Lineage, and Upbringing

Early life stress (ELS) is a potent developmental disruptor and increases the risk for psychopathology. Various forms of ELS have been studied in both humans and rodents, and have been implicated in altered DNA methylation, gene transcription, stress hormone levels, and behavior. Although recent studies have focused on stress-induced epigenetic changes, the extent to which ELS alters HPA axis function and stress responsivity across generations, whether these effects are sex-specific, and how lineage interacts with upbringing to impact these effects, remain unclear. To address these points, two generations of rodents were utilized, with the first generation subjected to ELS via maternal separation, and the second to a balanced cross-fostering paradigm. We hypothesized that ELS would disrupt normative development in both generations, manifesting as altered methylation and expression of genes associated with stress signaling pathways (Nr3c1, Nr3c2, and Bdnf), blunted corticosterone (CORT), and anxiety-like behaviors. Additionally, we expected deficits in the second generation to be modulated by caretaking environment and for the pattern of results to differ between the sexes. Results suggest that direct exposure to ELS leads to sex-specific effects on gene regulation and HPA functioning in adulthood, with maternal separation leading to increases in Bdnf methylation in both sexes, decreases in Bdnf expression in females, and decreases in Nr3c1 methylation in males, as well as blunted CORT and less anxiety-like behavior in females. These alterations converged with caretaking to impart perturbations upon the subsequent generation. Across sex, ELS lineage led to decreased methylation of Nr3c1, and increased methylation of Bdnf. In fostered animals, upbringing by a previously stressed mother interacted with offspring lineage to impact methylation of Nr3c1 and Bdnf. Upbringing was also implicated in altered anxiety-like behavior in males, and baseline CORT levels in females. Such effects may correspond with observed alterations in maternal behavior across groups. In conclusion, ELS conferred enduring sex-specific alterations, both first-hand and trans-generationally via lineage and upbringing. Importantly, lineage of cross-fostered pups was sufficient to normalize or disturb maternal behavior of foster-dams, an observation requiring further elucidation. These results have implications for multi-generational effects of ELS in humans and may motivate early interventions.

Long-term behavioural effects of maternal obesity in C57BL/6J mice

Diet is increasingly being recognised as an important contributor to mental health. A diet high in sugar and polyunsaturated fatty acids can have negative consequences for disease symptoms and outcomes in schizophrenia patients. There is also evidence that particular diets can have beneficial, therapeutic-like properties for human brain disorders. Additionally, dietary choices of mothers have been found to affect cognitive domains and anxiety behaviour of offspring. Here we investigated the effects of maternal high fat diet (HFD) on a variety of behavioural domains in offspring and also consider behaviours, which are schizophrenia-relevant. Female C57BL/6 J mice were fed HFD (N = 13) or chow (N = 11) from 6 weeks prior to mating, during gestation and lactation. The male offspring of these mothers were weaned onto chow on PND24 and underwent testing for a range of behavioural outcomes starting at 38 weeks of age. Offspring of HFD mothers were significantly heavier compared to those of control mothers from weaning and throughout the duration of the experiment. Offspring of HFD mothers had significantly improved sensorimotor gating compared to offspring of control mothers but showed no altered behavioural response in tests for cognition, sociability, locomotion or exploration. Future investigations are required to assess which HFD-induced factors are responsible for the effects, e.g. altered maternal nursing behaviour, altered gestational physiology, or others warrants further investigation.

Intergenerational transmission of maternal care deficiency and offspring development delay induced by perinatal protein malnutrition

Objectives: Early life represents a sensitive and critical period for an individual. Nutrition plays a crucial role in the maturation and functional development of the central nervous system. Inadequate nutrition before birth and during the postnatal life can seriously interfere with brain development and lead to behavioral and neurological disorders such as learning disabilities and psychiatric diseases. In addition, the quality of mother–infant interactions represents an important adaptive pathway that prepares offspring for the conditions of life. In this work, we asked if protein malnutrition alters maternal care and offspring development and if these phenotypes can be transmitted to next generation.Methods: Female mice were fed with a normal or hypoproteic diet during pregnancy and lactation. Nurturing behaviors, i.e. arched, blanket and passive nursing, and liking and grooming of the pups, were evaluated from postnatal day 1 (PD1) to postnatal day 7 (PD7). The same protocol was employed to evaluate maternal behavior for filial generation 1 (F1) and filial generation 2 (F2) dams. Offspring development was evaluated for F1, F2, and F3 generations. Developmental landmarks and neurological reflexes were assessed from PD8 until complete development of the landmark or acquisition of the reflex.Results: Our results show that malnourished dams provide a lesser and more fragmented maternal care than their normally fed counterparts. This altered maternal behavior as well as the delay in the physical and neurological development observed in the offspring from malnourished mothers was transmitted up to two generations at least.Conclusion: These results highlight the harmful effects of protein malnutrition even for generations that are not directly exposed to this environmental adversity.

Cafeteria diet during the gestation period programs developmental and behavioral courses in the offspring

The objective of this study was to investigate the effect of exposure to maternal consumption of a hyperenergetic, highly palatable diet, known as the cafeteria diet, during the gestation period on the development and behavior of offspring. For this, we used pregnant female mice that were fed a normal or a cafeteria diet during the gestation period. The evaluation of maternal behavior in lactating dams was performed from the second to the eighth day postpartum (PND 2-8). Weight gain, feed intake, and energy intake were recorded during the gestation period. In the offspring, reflex parameters and physical development were evaluated during the lactation period and when they reached adolescence. Behavioral performance was evaluated in light-dark, open-field, and play behavior tests. In addition, biochemical parameters of the dams and the adolescent offspring were evaluated. The cafeteria diet during gestation altered maternal behavior and the onset of physical and neurodevelopmental landmarks and had an impact on emotional and play behavior in adolescent offspring. In conclusion, our results demonstrate that exposure to maternal consumption of a cafeteria diet during the gestation period can program developmental and behavioral courses in the offspring.

Ghosts of mother's past: Previous maternal stress leads to altered maternal behavior following a subsequent pregnancy in rats.

A rodent model was used to explore whether mothers that experienced a postnatal stressor in the past (i.e., daily separations from her previous litter) exhibited altered maternal behavior during a typical, subsequent rearing experience. Stress-naïve female rats were bred and then separated from their pups (maternal separation) or remained with their pups (standard-rearing). After those pups were weaned, mothers were bred again with all pups from the subsequent litter being standard-reared. In the first week of life, various maternal behaviors directed towards these subsequent offspring were observed, including levels of nursing and pup retrieval. After weaning, mothers were tested for anxiety-like behavior, as well as memory on the object-recognition and object-placement tasks. The results show that previously stressed mothers retrieve their offspring significantly faster compared to mothers with no stress history, which may reflect a more "overprotective" mothering style. No other differences on maternal care were observed. Also, while previously stressed mothers were no more anxious than control mothers, they had impaired spatial memory on the object-placement task. This was not due to a general memory impairment as mothers performed equally on the object-recognition task, suggesting that previous maternal stress has specific effects on hippocampal-dependent tasks. That is, stress exerts lasting effects on types of behavior that are proposed to be beneficial to mothers and their offspring (i.e., efficient foraging and navigation abilities). Taken together, these results provide evidence that stress has specific and persistent effects on caregivers.

Combined effect of gestational stress and postpartum stress on maternal care in rats

Variations in maternal care in the rat influence the development of individual differences in behavioral and endocrine responses to stress. This study aimed to examine the interaction between intragastric intubation during late gestation and postpartum stress, induced by pup separation, on maternal behavior and on dams' emotional state and HPA axis function. Rats received intragastric intubation of water on days 12–20 of gestation or remained untreated in their home cage (naïve dams). Pup separation was used as a model of postpartum stress. The procedure consisted of a daily separation of the dam from its litter for 3h from PND 3 until PND 15. Pup separation was carried out in both naïve and intubated dams. The behavioral results indicate that the association of these two stressors significantly decreased arched-back nursing (ABN) and licking and grooming (LG), behaviors considered important parameters to discriminate the high quality of maternal care. Moreover, dams that received both stressors displayed less nest building and blanket nursing behaviors; no effect on the frequency of passive and total nursing was recorded. The analysis of single effects on ABN and LG, revealed that dams that underwent gestational stress induced by intragastric intubation displayed less LG, but ABN was overall unchanged. On the contrary, pup separation stress significantly increased ABN and LG upon reunion of naïve dams with their pups. Treatments per se or the association of both induced modest changes in plasma levels of allopregnanolone and corticosterone that likely did not influence maternal care. These data show that the association of a mild stress during gestation with an unfavorable experience after parturition had a significant impact on maternal care. This effect seems independent from HPA axis activation or from changes in emotional state; further studies would be necessary to ascertain the neural changes that could contribute to altered maternal behavior in stressed mothers. Moreover, these results suggest that the use of intragastric intubation during gestation would interfere with measures of drug-induced changes in maternal behavior and likely their consequences on the offspring.

Intergenerational accumulation of impairments in maternal behavior following postnatal social stress

Early adversity such as depressed maternal care can have long-term physiological and behavioral effects on offspring and future generations. Exposure to chronic social stress (CSS), an ethologically model of postpartum depression and anxiety, during lactation impairs maternal care and exerts similar effects on the F1 dam offspring of the stressed F0 dams. These changes associate with increased corticosterone and neuroendocrine alterations. CSS F2 offspring further display decreased social behavior as juveniles and adults and decreased basal levels of corticosterone. This current study investigates the intergenerational inheritance of alterations in maternal behavior in F2 CSS dams together with neuroendocrine and immune markers to explore whether aspects of maternal behavior are intergenerationally inherited through immune and neuroendocrine mechanisms. We find that defects in maternal care behavior persist into the F2 generation with F2 dams exhibiting a pervasively depressed maternal care and increased restlessness throughout lactation. This occurs together with reduced basal cortisol (in contrast to an increase in F1 dams), a lack of changes in neuroendocrine gene expression, and reduced serum ICAM-1 (intercellular adhesion molecule-1) levels - a marker for inflammation and blood–brain barrier integrity. The data support the hypothesis that the effects of chronic social stress can accumulate across multiple generations to depress maternal care, increase restlessness and alter basal functioning of the immune system and hypothalamic pituitary adrenal axis.

Plasticity in the olfactory bulb of the maternal mouse is prevented by gestational stress.

Maternal stress is associated with an altered mother-infant relationship that endangers offspring development, leading to emotional/behavioral problems. However, little research has investigated the stress-induced alterations of the maternal brain that could underlie such a disruption of mother-infant bonding. Olfactory cues play an extensive role in the coordination of mother-infant interactions, suggesting that motherhood may be associated to enhanced olfactory performances, and that this effect may be abolished by maternal stress. To test this hypothesis, we analyzed the impact of motherhood under normal conditions or after gestational stress on olfactory functions in C57BL/6 J mice. We report that gestational stress alters maternal behavior and prevents both mothers’ ability to discriminate pup odors and motherhood-induced enhancement in odor memory. We investigated adult bulbar neurogenesis as a potential mechanism of the enhanced olfactory function in mothers and found that motherhood was associated with an increased complexity of the dendritic tree of newborn neurons. This motherhood-evoked remodeling was totally prevented by gestational stress. Altogether, our results may thus provide insight into the neural changes that could contribute to altered maternal behavior in stressed mothers.

The performance and behaviour of gilts and their piglets is influenced by whether they were born and reared in farrowing crates or farrowing pens

The level of maternal care experienced by offspring in early life may influence their future behaviour. If maternal behaviour is influenced by the level of mother-young interaction in early life, this may persist in subsequent generations through altered maternal behaviour of female offspring. In the present study, post-farrowing behaviour of gilts and their piglets was observed in a crossover experiment. Gilts were born and reared in a farrowing crate (C) or in a pen with temporary confinement (P); and were observed after they farrowed in a crate or a pen with temporary confinement. Hence there were four experimental groups: CC (born and reared in a crate, farrowed in a crate, N =8), CP (born and reared in a crate, farrowed in a pen, N =6), PC (born and reared in a pen, farrowed in a crate N =5), and PP (born and reared in a pen, farrowed in a pen, N =8). Gilts and their piglets were observed for the first three days post-farrowing whilst they were all confined in crates. There were no differences between groups for total born, born alive, weaned per litter, or piglet mortality. Gilts in the PP group interacted more with neighbouring gilts/sows than any other (P<0.05). Gilts born and reared in pens touched their piglets more (Pborn =0.02) and vocalised more towards their piglets (Pborn = 0.01) than gilts born and reared in farrowing crates. Piglets born to PP gilts spent more time active in the creep area compared to all other groups (P<0.05). The current study demonstrated that the expression of some piglet-directed behaviour was influenced by the system in which a gilt was born and reared.

Does route of methamphetamine exposure during pregnancy have an impact on neonatal development and behaviour in rat offspring?

Many preclinical studies have aimed to elucidate the effects of methamphetamine (MA) exposure during pregnancy on the offspring in recent years. However, the severity of effects on the neonate may be related to the subcutaneous (sc) route of administration of the drug that is often employed (88% of preclinical studies) and consequently the delivered dose that the foetus is exposed to. To date there is a paucity of comparative studies investigating different routes of administration for MA during pregnancy and it is not known how these different routes compare when it comes to neonatal outcome. Thus, the aim of this study was to determine if the route of administration of MA (oral gavage or sc injection) during pregnancy at a pharmacological dose affects the magnitude of neurodevelopmental and behavioural effects in the resultant rat offspring. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (3.75mg/kg) or control (distilled water) via oral gavage or sc injection from gestation day 7–21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. When administered sc, MA significantly reduced maternal weight gain and altered maternal behaviour; mothers spent less time in the nest with pups and spent less time nursing compared to controls. Significant impairments in neurodevelopmental parameters were evident in both MA treatment groups. Somatic development such as pinna unfolding, fur appearance and eye opening were all delayed after MA exposure but these impairments were more pronounced in the MA sc group. Other somatic parameters such as ano-genital distance and body length were only impeded by sc MA. Behavioural development in the surface righting, inclined plane and forelimb grip tests were also altered for both MA treatment groups. This study demonstrates that prenatal MA can have a profound effect on neonatal outcome, but this can be exacerbated if given via the subcutaneous route, as well as producing additional effects not seen with the oral gavage route. Consequently, the route of administration should be considered when interpreting preclinical studies investigating prenatal MA exposure.