Cross-fostering Procedure Research Articles

Microbial modulation via cross-fostering prevents the effects of pervasive environmental stressors on microglia and social behavior, but not the dopamine system.

Environmental toxicant exposure, including air pollution, is increasing worldwide. However, toxicant exposures are not equitably distributed. Rather, low-income and minority communities bear the greatest burden, along with higher levels of psychosocial stress. Both air pollution and maternal stress during pregnancy have been linked to neurodevelopmental disorders such as autism, but biological mechanisms and targets for therapeutic intervention remain poorly understood. We demonstrate that combined prenatal exposure to air pollution (diesel exhaust particles, DEP) and maternal stress (MS) in mice induces social behavior deficits only in male offspring, in line with the male bias in autism. These behavioral deficits are accompanied by changes in microglial morphology and gene expression as well as decreased dopamine receptor expression and dopaminergic fiber input in the nucleus accumbens (NAc). Importantly, the gut-brain axis has been implicated in ASD, and both microglia and the dopamine system are sensitive to the composition of the gut microbiome. In line with this, we find that the composition of the gut microbiome and the structure of the intestinal epithelium are significantly shifted in DEP/MS-exposed males. Excitingly, both the DEP/MS-induced social deficits and microglial alterations in males are prevented by shifting the gut microbiome at birth via a cross-fostering procedure. However, while social deficits in DEP/MS males can be reversed by chemogenetic activation of dopamine neurons in the ventral tegmental area, modulation of the gut microbiome does not impact dopamine endpoints. These findings demonstrate male-specific changes in the gut-brain axis following DEP/MS and suggest that the gut microbiome is an important modulator of both social behavior and microglia.

Effect of within-litter birth weight variation after cross-fostering on piglet preweaning growth and mortality.

Cross-fostering is commonly used in commercial swine production to equalize litter sizes and/or adjust piglet birth weights within litters. However, there is limited published information on optimum cross-fostering procedures. This study evaluated the effects of within-litter birth weight variation after cross-fostering (using litters of 14 piglets) on piglet preweaning mortality (PWM) and weaning weight (WW). An RCBD was used (blocking factors were day of farrowing and sow parity, body condition score, and functional teat number) with an incomplete factorial arrangement of the following two treatments: 1) birth weight category (BWC): light (<1.0 kg), medium (1.0 to 1.5 kg), or heavy (1.5 to 2.0 kg); 2) litter composition: uniform, all piglets in the litter of the same BWC [uniform light (14 light piglets); uniform medium (14 medium piglets); uniform heavy (14 heavy piglets)]; mixed, piglets in the litter of two or more BWC [L+M (seven light and seven medium piglets); M+H (seven medium and seven heavy piglets); L+M+H (three light, six medium, and five heavy piglets)]. Piglets were weighed at 24 h after birth and randomly allotted to litter composition treatment from within BWC; all piglets were cross-fostered. There were 47 blocks of six litters (total 282 litters and 3,948 piglets). Weaning weights were collected at 18.7 ± 0.64 d of age; all PWM was recorded. Individual piglet WW and PWM data were analyzed using PROC MIXED and PROC GLIMMIX of SAS, respectively; models included fixed effects of BWC, litter composition, and the interaction, and random effects of sow within the block. There was litter composition by BWC interactions (P ≤ 0.05) for WW and PWM. Within each BWC, WW generally increased and PWM generally decreased as littermate weight decreased. For example, WW was greatest (P ≤ 0.05) for light piglets in uniform light litters, for medium piglets in L+M litters, and for heavy piglets in L+M+H litters. Preweaning mortality was lowest (P ≤ 0.05) for medium piglets in L+M litters, and for heavy piglets in L+M+H litters; however, litter composition had no effect (P > 0.05) on PWM of light piglets. In conclusion, increasing the average birth weight of littermates after cross-fostering generally decreased WW and increased PWM for piglets of all birth weight categories. This implies that the optimum approach to cross-fostering that maximizes piglet preweaning growth and survival is likely to vary depending on the birth weight distribution of the population.

Within-Family Environment and Cross-Fostering Stress Affect Behavior and Physiology in Wild Cavies (Cavia aperea).

Stability of personality traits is well-documented for a wide variety of animals. However, previous results also suggest that behavioral phenotypes are plastic during early ontogeny and can be adaptively shaped to the social environment. In cavies (Cavia aperea), it has already been documented that the size at birth relative to siblings (size rank) greatly influences various behavioral and physiological traits that last at least until independence. The aim of the current study was (1) to investigate if behavioral and physiological differences between pups of the same litter persist until after independence and influence development long-lasting, (2) to determine the potential plasticity in response to changes in the early within-family environment by cross-fostering pups either to the same, a lower, or a higher size rank in a foster-family. We measured three behavioral traits (number of interactions with a novel object, distance moved in an open field, struggle docility) and two physiological traits (resting metabolic rate and basal cortisol levels). We predicted that cross-fostering into a litter where pups occupy the same size rank would not change the expression of traits. Cross-fostering to a different size rank should not influence the expression of traits if repeatability measures indicate low plasticity. Alternatively, if the traits are plastic, animals should adjust trait expression to fit with the size rank occupied in the foster litter. Initial differences in struggle docility, distance moved in an open field and in baseline cortisol concentration between pups of different size-ranks did not remain stable beyond independence. In addition, we found remarkable plasticity of the measured traits in response to cross-fostering to the same, a smaller or larger size-rank, suggesting that differences between pups are more the result of social constraints leading to adaptive shaping of individual phenotypes within a family. We also found a significant influence of the cross-fostering procedure itself. Cross-fostered individuals were less bold, grew slower and showed elevated resting metabolic rates. This finding suggests a cautious interpretation of previous cross-fostering studies and stresses the need for proper control groups to reliably separate the effect of cross-fostering per se from those induced by an experimental treatment.

Maternal care exerts disease-modifying effects on genetic absence epilepsy and comorbid depression.

WAG/Rij rats, a genetic animal model of absence epilepsy with comorbidity of depression, exhibit behavioral depression-like symptoms and spontaneous generalized spike-wave discharges (SWDs) in the EEG at the age of 6 to 8 months. The aim of the present study was to test the hypothesis that maternal care is an environmental factor which, along with genetic predisposition, may contribute to the expression of absence seizures and depression-like comorbidity later in life. To achieve this, a cross-fostering procedure was used. EEG and behavior in the forced swimming test were analyzed in WAG/Rij and Wistar offspring reared by their own mothers (non-cross-fostered), foster mothers of the same strain (in-fostered) or another strain (cross-fostered) at the age of 7 to 8 months. Maternal care and forced swimming test behavior were assessed in the dams. WAG/Rij mothers showed depression-like behavior and reduced maternal care irrespective of litter size and litter composition (own or foster pups) compared with Wistar dams. WAG/Rij offspring reared by Wistar dams with a high level of maternal care exhibited less and shorter SWDs and reduced depression-like comorbidity in adulthood compared with age-matched WAG/Rij offspring reared by their own or foster WAG/Rij mothers with a low level of maternal care. Moreover, rearing by Wistar mothers delayed the onset of absence epilepsy in WAG/Rij rats. Adoption by WAG/Rij dams did not change EEG and behavior in Wistar rats. Our study demonstrates that improvement of early care-giving environment can be used as a disease-modifying treatment to counteract epileptogenesis and behavioral comorbidities in genetic absence epilepsy.

Unstable Maternal Environment Affects Stress Response in Adult Mice in a Genotype-Dependent Manner.

Early postnatal events exert powerful effects on development, inducing persistent functional alterations in different brain network, such as the catecholamine prefrontal-accumbal system, and increasing the risk of developing psychiatric disorders later in life. However, a vast body of literature shows that the interaction between genetic factors and early environmental conditions is crucial for expression of psychopathologies in adulthood. We evaluated the long-lasting effects of a repeated cross-fostering (RCF) procedure in 2 inbred strains of mice (C57BL/6J, DBA/2), known to show a different susceptibility to the development and expression of stress-induced psychopathologies. Coping behavior (forced swimming test) and preference for a natural reinforcing stimulus (saccharine preference test) were assessed in adult female mice of both genotypes. Moreover, c-Fos stress-induced activity was assessed in different brain regions involved in stress response. In addition, we evaluated the enduring effects of RCF on catecholamine prefrontal-accumbal response to acute stress (restraint) using, for the first time, a new "dual probes" in vivo microdialysis procedure in mouse. RCF experience affects behavioral and neurochemical responses to acute stress in adulthood in opposite direction in the 2 genotypes, leading DBA mice toward an "anhedonic-like" phenotype and C57 mice toward an increased sensitivity for a natural reinforcing stimulus.

EPA-1266 – Anxiety behavior extinction is influenced by early environment in a genetic background-dependent way

Introduction Several factors influence the emotional behavior, including environment, genetic and the interaction between them. Objective The aim of this work is to investigate the interaction between environmental and genetic influences in the divergent behavior of Carioca High and Low Freezing (CHF and CLF) rats - a genetic model to study fear and anxiety. The Carioca rat lines were produced from selective breeding method, from animals with the highest and lowest levels of freezing behavior in the contextual fear conditioning, a model to study anxiety-like behavior. Methods To investigate the gene-environment interplay, we employed the cross-fostering procedure, which CHF rat pups were raised by CLF dams, and vice-versa, since pos natal day (PND) 1 until weaning at PND21. The litters were culled in 8 pups, and we fostered only 2–3 male pups per litter. We also maintained CHF and CLF control, no-fostered litters. On PND60, male animals of the four groups (CHF (n=7), CHF-CLF (CHF pups raised by CLF dams) (n=6), CLF (n=4) and CLF-CHF (n=3)) were exposed to the contextual fear conditioning. Results The freezing behavior on the day after foot shocks was analyzed. A two-way ANOVA showed that, although CHF rats had a higher time in freezing in this task comparing to the CLF (p CLF-CHF = CLF. On PND120, the same male rats were exposed to a 12-minutes-session, two-session extinction paradigm, in the same context. In these sessions, no foot shock was used. Comparing the freezing time in the context session on the conditioning paradigm to the freezing time on the first extinction session, we observed a significant decrease in this behavior for the CHF-CLF group, but not in the CHF group (p Conclusions This data suggest an existence of an early environment influence in the anxiety behavior extinction, but it was dependent of the genetic background.

Effects of early traumatic experience on vocal expression of emotion in young female rhesus macaques

The present study used a cross-fostering procedure to investigate the effects of early traumatic experience on vocal expressions of emotions in rhesus macaques (Macaca mulatta). The subjects of the study were 12 juvenile females: six were born to abusive mothers and reared by nonabusive controls, and six were born to controls and reared by abusive mothers. The cross-fostering took place within 24-48 hr after birth. Vocalizations were recorded from the subjects in their social groups during their first 2 years of life. Abusive mothers maltreated their adopted daughters in the first 2-3 months after birth with patterns similar to those previously shown with their biological offspring. Abused females produced proportionally more noisy screams compared to controls. While controls used noisy screams during contact aggression and tonal screams during non-contact aggression, the screams from the abused animals appeared to be distributed equally across contexts. Acoustical analyses revealed that the screams of the abused females were less modulated and had lower fundamental frequencies compared to the screams of controls. Taken together, these results suggest that traumatic experience in the first few months of life can have long-term effects on vocal emotional expression in rhesus macaques.

Maternal care counteracts behavioral effects of prenatal environmental stress in female rats

There is extensive evidence in rats that prenatal environmental stress (PES) exposure and early postnatal altered maternal care, as a consequence of stress during gestation, can detrimentally affect the brain and behavioral development of the offspring. In order to separate the effect of PES on the fetuses from that on the behavior of the mother, in the present study, we used a cross-fostering procedure in which PES-fetuses were raised by non-stressed mothers and non PES-fetuses were raised by stressed mothers. In Experiment 1, non-stressed mothers showed significantly more maternal behavior than stressed mothers. In Experiment 2, when the female offspring from Experiment 1 reached maturity, they were tested for: (1) induced maternal behavior (MB), (2) plasma levels of corticosterone (Cpd B), progesterone (P), and estradiol (E 2), (3) number of accessory olfactory bulb (AOB) mitral cells, and (4) c-fos expression measured in AOB and medial preoptic area (MPOA) neurons. We replicated our previous findings that the PES group reared by their own stressed mothers, when adult, attacked the young, expressed disorganized MB and showed altered Cpd B, P and E 2 levels, plus a male-like neuro-morphological pattern in the AOB, by comparison with the non-PES group, reared by their own non-stressed mothers. By contrast, when adult, the PES group reared by non-stressed mothers showed hormonal and morphological neuronal alterations, but they displayed appropriate (full) MB. The non-PES group raised by stressed mothers also showed altered hormone levels, but showed full MB and no morphological neuronal changes. Significant differences in the AOB and MPOA c-fos activity, related to whether or not MB was expressed, were found in the non-PES groups, but not in the PES group reared by non-stressed mothers. To our knowledge, this is the first study to document that adequate maternal care, early in development, can shape the subsequent expression of induced MB, overcoming neuro-morphological and hormonal alterations that are produced by prenatal environmental stress. We conclude that maternal care during early postnatal development can counteract detrimental effects of prenatal environmental stress, exerting long-lasting effects that modulate the behavioral phenotype of the offspring.

Genotype rather than non-genetic behavioural transmission determines the temperament of Merino lambs

AbstractMerino ewes have been selected, over 18 generations, for calm (C) or nervous (N) temperament using using an arena test and an isolation box test. We investigated the relative contributions of genotype versus the post-partum behaviour of the dam on the temperament of the lambs using a cross-fostering procedure. Forty-eight multiparous calm and 52 nervous ewes were artificially inseminated with the semen of a sire of the same temperament. At birth, 32 lambs of a given temperament line were cross fostered to ewes from the other line (16 N × C, 16 C × N), 34 lambs were cross fostered to ewes from the same line (15 C × C, 19 N × N) and 30 lambs were left with their birth mother (15 C, 15 N), to control for the effect of cross fostering. The temperament of the progeny was assessed at two occasions, one week after birth by measuring locomotor activity during an open-field test and at weaning (16 weeks) by measuring locomotor activity during an arena test and agitation score measured during an isolation box test. There was a genotype effect but no maternal or fostering effect on the lamb temperament at one week. This may be because the maternal behaviour of the foster ewes did not differ considerably between the calm and nervous mothers during adoption or within the first week, post partum. Similarly, at weaning, only a genotype effect was found on the locomotor and agitation score. Therefore, it appears that temperament in Merino sheep is mainly determined by the genetic transmission of the trait across generations rather than behaviours learned from the mother.

Home seeking behavior in rat pups: Attachment vs. kin selection, oxytocin vs. vasopressin

We are interested in the rat as an animal model for infant–mother attachment. In the first experiment we tried to distinguish between a preference for familiar animals (attachment theory) and a preference for genetically related animals (kin selection theory) with the use of an early cross-fostering procedure. Genetic relationships did not influence preferences in cross-fostered pups on postnatal day17, only familiarity did. Subsequently we investigated if peptides known to influence affiliative behaviors were also effective in the present paradigm. Injection of oxytocin into the cisterna magna did not yield significant effects on preference, while vasopressin and desglycinamide-[Arg8]vasopressin reduced the preference in a dose dependent manner. The effect of vasopressin was completely blocked by pretreatment with the vasopressin V 1A receptor antagonist d(CH 2) 5Tyr(Me) 2,Arg 8-vasopressin. We discuss the explanatory power of attachment theory and kin selection theory with regard to preference experiments in rats and the usefulness of the rat as an animal model for infant–mother attachment.

Maternal Environment Alters Social Interactive Traits But Not Open-Field Behavior in Fischer 344 Rats

Although it is recognized that the genetic background governs behavioral phenotypes, environmental factors also play a critical role in the development of various behavioral processes. The maternal environment has a major impact on pups, and the cross-fostering procedure is used to determine the influence of early life experiences. The present study examined the influence of maternal environment on behavioral traits in inbred Fischer 344 (F344) rats. F344/DuCrlCrlj and Wistar (Crlj:WI) pups were fostered from postnatal day 1 as follows: Wistar pups raised by Wistar dams, F344 raised by Wistar, Wistar raised by F344, and F344 raised by F344. At 10 weeks of age, rats were randomly assigned to an open-field test and social interaction test. In the open-field test, irrespective of the rearing conditions, the activity during the first 1 min was significantly lower in F344 rats than in Wistar rats. Latency to the onset of movement showed no difference between groups. In the social interaction test, the recognition performance during the first 1 min in F344 raised by F344 was significantly shorter than that in the other groups. The onset of recognition to a novel social partner in F344 raised by F344 was significantly delayed, and the delay disappeared upon cross-fostering by Wistar dams. These results raise the possibility that the behavioral phenotype of F344 rats results from the interplay of genetic factors and maternal environment during early life, and that F344 rats are a strain with high susceptibility to rearing conditions for the formation of their emotionality.

Assessment of the perinatal effects of maternal ingestion of Ipomoea carnea in rats

It is believed that Ipomoea carnea toxicosis induces abnormal embryogenesis in livestock. Studies on rats treated with I. carnea aqueous fraction (AF) during gestation, revealed litters with decreased body weight, but the characteristic vacuolar lesions promoted by swainsonine, its main toxic principle, were observed only in young rats on postnatal day (PND) 7. However, these alterations could have resulted as consequence of swainsonine placental passage and/or damage or even ingestion of the contaminated milk by pups. Thus, this perinatal work was performed to verify the transplacental passage of swainsonine and its excretion into milk employing the cross-fostering (CF) procedure as a tool of study. Females were treated with AF or vehicle during gestation and after birth pups were fostered between treated and untreated dams. Pup body weight gain (BWG) and histopathology to observe vacuolar degeneration were performed on PND 3 and 7. In addition, swainsonine detection was performed in amniotic fluid and milk from rats treated with the AF during gestation or lactation. BWG was significantly lower only in pups from mothers treated with the plant and fostered to other treated mothers (AF–AF group of pups). The histopathology revealed that pups from treated mothers fostered to untreated ones showed the characteristic vacuolar lesions; however, the lesions from the AF–AF pups were more severe in both periods evaluated. Amniotic fluid and milk analysis revealed the presence of swainsonine excretion into these fluid compartments. Thus, the results from CF and the chemical analysis allowed concluding that swainsonine passes the placental barrier and affects fetal development and milk excretion participates in I. carnea perinatal toxicosis.

Case studies of song and call learning by a hybrid Bengalese–Zebra Finch and Bengalese-fostered Zebra Finches: Assessing innate factors in vocal learning

Vocal learning in birds is limited by both genetic and environmental factors. Innately determined, species-specific ranges of song parameters restrict song structures; the actual parameter values are determined by environmental inputs during learning. This is also true for some call notes. Here, we investigated the characteristics of songs and distance calls in a hybrid Bengalese–Zebra Finch and Bengalese-fostered Zebra Finches. The Bengalese-fostered Zebra Finches learned a limited part of the song elements, whereas the hybrid learned most of the foster father's song. However, the hybrid could not learn the acoustic morphology of Bengalese distance calls as well as the fostered finches. The results suggest that the neural circuitry for song element repertoire and call acoustic morphology are independent and that hybridization and cross-fostering procedures are useful tools for investigating genetic and environmental factors in vocal learning.

Genetic aspects of mother-offspring conflict in rhesus macaques

This study investigated the occurrence of mother-offspring conflict in rhesus macaques and possible genetic correlations between maternal and offspring conflict-related behavior, using a cross-fostering procedure and a developmental approach. Ten female infants were cross-fostered at birth and observed with their foster mothers during their 1st year of life. Data on the infants’ biological mothers were also available. In the 1st 3 months of infant life, there was little or no mother-infant conflict over time spent in contact. Correlations between infant behavior and the behavior of foster mothers in this period likely resulted from individual differences in infant activity levels and maternal concerns for safety or maternal attempts to encourage infant independence. During the mating season, when infants were 7–9 months old, conflict over time spent in contact became apparent. Infant conflict-related behavior was not predicted by their foster mothers’ behavior but by the behavior of their biological mothers. These findings concur with those of recent studies in other animal taxa in suggesting that conflict-related behavioral traits may be genetically correlated in mothers and offspring and that the latter may be engaged in a runaway selection process that would result in the escalation of conflict.

Interacting effects of oxazepam in late pregnancy and fostering procedure on mouse maternal behavior

The present study was designed to assess the proactive effects of late pregnancy benzodiazepine (BDZ) treatment on maternal behavior in the postpartum period, using cross-fostering procedures to control for the role of changes produced prenatally in the offspring. Outbred CD-1 mouse dams were treated with either oxazepam (OX, 15 mg/kg PO twice/day on pregnancy days 12-16) or vehicle (VEH). After parturition, entire litters were exchanged either within treatments (in-fostered groups, IF) or between treatments (cross-fostered groups, CF), while additional litters were left undisturbed (un-fostered groups, UF). The behavior of lactating dams was observed in their home cages at 4, 8, and 12 days postpartum. Maternal responses, particularly nursing, were reduced in the OX-UF and OX-CF conditions and either normal or enhanced in the OX-IF condition. Correspondingly, locomotor/exploratory activity was markedly enhanced in the former conditions and close to the control level in the latter condition. In sum, the fostering variable appeared to determine whether pups raised by dams treated previously with BDZ receive either insufficient or exaggerated maternal care. This points to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on offspring development.

Mother-offspring interaction and pup development in genetically deaf mice.

The role of ultrasonic calls emitted by pups on maternal behavior has been investigated by using genetically deaf (dn/dn) and normal-hearing (+/+) mice of the GFF strain. The behavior and the sensory-motor development of unfostered and cross-fostered pups, as well as the behavior of the mothers, was analyzed. Deaf pups emitted fewer ultrasonic calls than pups with normal hearing. The cross-fostering procedure decreased the amount of vocalizations produced by normal pups, thus stressing the reinforcement effect of maternal behavior on pups' ultrasonic communication. No difference in maternal behavior emerged between deaf and normal-hearing mothers toward their pups. However, cross-fostered pups received less maternal care than pups raised by their natural mothers, this effect being more evident in deaf pups reared by mothers with normal hearing, than vice versa. Deafness, in both mothers and pups, seemed to be associated with increased locomotor activity, possibly to offset their auditory handicap in mother-offspring relationships. Furthermore, deaf pups showed a faster gain in weight than normal pups, this capability being affected by the genotype of the rearing parent. On the whole, these data could suggest that maternal behavior in deaf mice has became independent of ultrasonic stimuli emitted by the pups. Other biobehavioral characteristics of deaf mice indicate a more active role played by these pups in mother-offspring interaction in comparison with pups with normal hearing.

Differences in patterns of pup care in mice V—Pup ultrasonic emissions and pup care behavior

Newborn mice, like all newborn rodents, are able to emit high frequency signals, in particular when they are put out of the nest. Moreover, it is known that in this situation retrieving behaviors are induced in the foster mother, which are likely to reveal stable differences across inbred strains of mice. The question that arises is whether these differences are causally linked to differences in the pup rate of signalling and/or to the capacity of the females of these strains to perceive them. To provide insights into this question, the behavior of 8 inbred strains of mice was observed: A/J, BALB/c, CBA/H, C57BL/6, C57Br, DBA, NZB and XLII. (1) Pup ultrasonic calls of each of these strains, emitted in the same conditions as a retrieving test, were recorded and tabulated. (2) Auditory sensitivities of females belonging to these strains were determined by auditory evoked potentials recorded in the inferior colliculus. (3) These two variables were analysed in relation to scores of females of these strains on three variables of a retrieving test. Results show that the presence of other factors than auditory cues must be taken into account to describe differences across strains in retrieving performances. (4) This conclusion has been confirmed by results obtained using cross-fostering procedure. Female mice unable to utilize ultrasonic information may use other sensory channels. Furthermore, female mice capable of perceiving ultrasounds may also be able to use different sensory modalities in different situations.

Y-chromosome length in sublines of two mouse strains.

Differences in intermale aggression have been repeatedly reported for DBA/1 and C57BL/10 mice. The results of rreciprocal crosses combined with cross-fostering procedures suggest an involvement of the Y chromosome. In the present study, the length of the Y chromosome relative to that of chromosome 19 was ascertained in five sublines of DBA/1Bg, three sublines of C57BL/10Bg, and C57BL/10.DBA/1-Y congenic stock of mice, which carries the DBA/1Bg Y chromosome. With respect to the length of the Y chromosome relative to that of chromosome of 19, two of the DBA/1 sublines are shorter than the other three DBA/1 sublines, and all DBA/1 sublines are shorter than the three C57BL/10 sublines. This is attributable primarily to the length of the Y chromosome. The C57BL/10 sublines and the BL10.D1-Y congenic stock tested exhibit the same relative lengths of the Y chromosome, suggesting that its length has changed on the C57BL/10 genetic background. There is a parallel dependence on autosomal background of the effect of the Y chromosome on intermale aggression.

Perinatal naloxone: When does naloxone affect hyperalgesia?

Pregnant mice were treated with naloxone via subcutaneous implants, from about 5 days prior to parturition. At birth entire litters were cross-fostered so that groups of offspring were exposed to naloxone treated mothers; before birth, after birth to weaning, from about 5 days prior to birth to weaning, or not exposed to naloxone. When tested on a hot-plate at 50 days of age, females either prenatally treated or treated pre- and postnatally showed hyperalgesia to heat. For males, this effect was not evident. This sex difference may have been induced by the cross-fostering procedure.

Response model analysis for cross-fostering studies: Prenatal versus postnatal effects on offspring exposed to methylmercury dicyandiamide

Quantitation of prenatal versus postnatal effects in offspring derived from treated mothers requires both cross-fostering procedures and a cogent method of data analysis. An explicit statement of the manner in which the treatments (independent variables) combine to produce the observed development parameters (dependent variables) is defined as the response model. We present the response model approach to analysis of these cross-fostering designs and the application of multiple regression to their solution. Pregnant 129 SvSl mice received single ip injections of 0, 4, or 8 mg/kg of methylmercury dicyandiamide (MeHg) on Day 7, 9, or 12 of gestation. Fostering and cross-fostering procedures were carried out at birth to partition the effects of prenatal and postnatal exposure on two parameters: survival and weight gain. A linear response model is presented to aid in: (1) conceptualizing the cross-fostering process; (2) quantitating the effects of treatment day, maternal dose, and the fostering process; and (3) providing the basis for statistical analysis. A multiple regression method is described to provide analysis of variance, solution for model parameters, and a guide in model simplification and statistical testing. Cross-fostering procedures permitted partitioning of adverse effects into prenatal and postnatal components. Effects of prenatal exposure to MeHg were about twice as large as postnatal and were greatest when administered late in the period of organogenesis. The dose response was approximately linear (proportional) in weight and logarithmic in survival. Thus, doses of MeHg which had no apparent effect on pregnant female mice did result in reduced survival to weaning and weight gain of offspring.