Impact of a bisphenol A, F, and S mixture and maternal care on the brain transcriptome of rat dams and pups.

Products containing BPA structural analog replacements have increased in response to growing public concern over adverse effects of BPA. Although humans are regularly exposed to a mixture of bisphenols, few studies have examined effects of prenatal exposure to BPA alternatives or bisphenol mixtures. In the present study, we investigate the effect of exposure to an environmentally-relevant, low-dose (150 ug/kg body weight per day) mixture of BPA, BPS, and BPF during gestation on the brain transcriptome in Long-Evans pups and dams using Tag RNA-sequencing. We also examined the association between dam licking and grooming, which also has enduring effects on pup neural development, and the transcriptomes. Associations between licking and grooming and the transcriptome were region-specific, with the hypothalamus having the greatest number of differentially expressed genes associated with licking and grooming in both dams and pups. Prenatal bisphenol exposure also had region-specific effects on gene expression and pup gene expression was affected more robustly than dam gene expression. In dams, the prelimbic cortex had the greatest number of differentially expressed genes associated with prenatal bisphenol exposure. Prenatal bisphenol exposure changed the expression of over 2000 genes in pups, with the majority being from the pup amygdala. We used Gene Set Enrichment Analysis (GSEA) to asses enrichment of gene ontology biological processes for each region. Top GSEA terms were diverse and varied by brain region and included processes known to have strong associations with steroid hormone regulation, cilium-related terms, metabolic/biosynthetic process terms, and immune terms. Finally, hypothesis-driven analysis of genes related to estrogen response, parental behavior, and epigenetic regulation of gene expression revealed region-specific expression associated with licking and grooming and bisphenol exposure that were distinct in dams and pups. These data highlight the effects of bisphenols on multiple physiological process that are highly dependent on timing of exposure (prenatal vs. adulthood) and brain region, and reiterate the contributions of multiple environmental and experiential factors in shaping the brain.

Social status mediated variation in hypothalamic transcriptional profiles of male mice.

Animals of different social status exhibit variation in aggression, territorial and reproductive behavior as well as activity patterns, feeding, drinking and status signaling. This behavioral and physiological plasticity is coordinated by underlying changes in brain gene transcription. Using Tag-based RNA sequencing (Tag-seq), we explore RNA transcriptomes from the medial preoptic area (mPOA) and ventral hypothalamus (vHYP) of male mice of different social ranks in a dominance hierarchy and detect candidate genes and cellular pathways that underlie status-related plasticity. Within the mPOA, oxytocin (Oxt) and vasopressin (Avp) are more highly expressed in subdominant mice compared to other ranks, while nitric oxide synthase (Nos1) has lower expression in subdominant mice. Within the vHYP, we find that both orexigenic and anorexigenic genes involved in feeding behavior, including agouti-related peptide (Agrp), neuropeptide-Y (Npy), galanin (Gal), proopiomelanocortin (Pomc), and Cocaine- and Amphetamine-Regulated Transcript Protein prepropeptide (Cartpt), are less expressed in dominant animals compared to more subordinate ranks. We suggest that this may represent a reshaping of feeding circuits in dominant compared to subdominant and subordinate animals. Furthermore, we determine several genes that are positively and negatively associated with the level of despotism (aggression) in dominant males. Ultimately, we identify hypothalamic genes controlling feeding and social behaviors that are differentially transcribed across animals of varying social status. These changes in brain transcriptomics likely support phenotypic variation that enable animals to adapt to their current social status.

Behavioural and physiological plasticity in social hierarchies.

Individuals occupying dominant and subordinate positions in social hierarchies exhibit divergent behaviours, physiology and neural functioning. Dominant animals express higher levels of dominance behaviours such as aggression, territorial defence and mate-guarding. Dominants also signal their status via auditory, visual or chemical cues. Moreover, dominant animals typically increase reproductive behaviours and show enhanced spatial and social cognition as well as elevated arousal. These biobehavioural changes increase energetic demands that are met via shifting both energy intake and metabolism and are supported by coordinated changes in physiological systems including the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes as well as altered gene expression and sensitivity of neural circuits that regulate these behaviours. Conversely, subordinate animals inhibit dominance and often reproductive behaviours and exhibit physiological changes adapted to socially stressful contexts. Phenotypic changes in both dominant and subordinate individuals may be beneficial in the short-term but lead to long-term challenges to health. Further, rapid changes in social ranks occur as dominant animals socially ascend or descend and are associated with dynamic modulations in the brain and periphery. In this paper, we provide a broad overview of how behavioural and phenotypic changes associated with social dominance and subordination are expressed in neural and physiological plasticity. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.

[Health Ethics in Benin and HIV-AIDS : What are the stakes]. / Chapitre 5. L?éthique en santé au Bénin et le vih-sida : quels enjeux.

As part of the fight against HIV-AIDS, an effort was made at the ethical component, namely that there are legal texts, institutional and ethical. There are ethics committees (three) that give reasoned opinions on study protocols and are endeavoring to raise awareness of the actors. But we note that there is not yet a real ownership and adoption of ethical practice by them. This study targeted research projects on HIV-AIDS and centers supported PLHIV in order to analyze ethical issues : 1) the method of recruitment of participants and beneficiaries ; 2) obtaining informed consent from them ; 2) measures of confidentiality and anonymity ; 3) the integrity of staff of these projects and centers and conflicts of interest. A thematic analysis of data collected, which is done, after semi-structured interviews, helped to highlight the issues related to the recruitment process, obtaining informed consent, confidentiality measures and anonymity, integrity and Conflict of Interest. Let us remember that what is done, not done yet in the forms of art. Constant monitoring is called for, as leaders with ethics committees.They are supposed to play fully their roles.

The functional serotonin 1a receptor promoter polymorphism, rs6295, is associated with psychiatric illness and differences in transcription.

The G/C single-nucleotide polymorphism in the serotonin 1a receptor promoter, rs6295, has previously been linked with depression, suicide and antidepressant responsiveness. In vitro studies suggest that rs6295 may have functional effects on the expression of the serotonin 1a receptor gene (HTR1A) through altered binding of a number of transcription factors. To further explore the relationship between rs6295, mental illness and gene expression, we performed dual epidemiological and biological studies. First, we genotyped a cohort of 1412 individuals, randomly split into discovery and replication cohorts, to examine the relationship between rs6295 and five psychiatric outcomes: history of psychiatric hospitalization, history of suicide attempts, history of substance or alcohol abuse, current posttraumatic stress disorder (PTSD), current depression. We found that the rs6295G allele is associated with increased risk for substance abuse, psychiatric hospitalization and suicide attempts. Overall, exposure to either childhood or non-childhood trauma resulted in increased risk for all psychiatric outcomes, but we did not observe a significant interaction between rs6295 and trauma in modulating psychiatric outcomes. In conjunction, we also investigated the potential impact of rs6295 on HTR1A expression in postmortem human brain tissue using relative allelic expression assays. We found more mRNA produced from the C versus the G-allele of rs6295 in the prefrontal cortex (PFC), but not in the midbrain of nonpsychiatric control subjects. Further, in the fetal cortex, rs6295C allele exhibited increased relative expression as early as gestational week 18 in humans. Finally, we found that the C:G allelic expression ratio was significantly neutralized in the PFC of subjects with major depressive disorder (MDD) who committed suicide as compared with controls, indicating that normal patterns of transcription may be disrupted in MDD/suicide. These data provide a putative biological mechanism underlying the association between rs6295, trauma and mental illness. Moreover, our results suggest that rs6295 may affect transcription during both gestational development and adulthood in a region-specific manner, acting as a risk factor for psychiatric illness. These findings provide a critical framework for conceptualizing the effects of a common functional genetic variant, trauma exposure and their impact on mental health.

Postnatal maternal care predicts divergent weaning strategies and the development of social behavior.

Maternal care experienced during postnatal development predicts long-term neurobiological and behavioral outcomes. However, the cascade of behavioral changes that emerge in response to maternal care has not been elucidated. In the current study, we examine naturally occurring variation in postnatal licking/grooming (LG) in C57BL/6J mice to determine its impact on preweaning maternal and pup behavior, the weaning process, the pace of developmental change, the emergence of social behavior, and indices of anxiety-like behavior in adulthood. Our analyses indicate that lower postnatal LG is associated with truncated and more infrequent maternal behavior during the preweaning period. Moreover, compared to High LG dams, Low LG dams are observed to actively wean their offspring sooner and have offspring that play more frequently. The heightened pace of developmental change observed in offspring of Low LG dams suggests a more rapid transition to behavioral and nutritional independence, which could have implications for future reproductive strategies.

Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation.

Prenatal maternal psychological distress increases risk for adverse infant outcomes. However, the biological mechanisms underlying this association remain unclear. Prenatal stress can impact fetal epigenetic regulation that could underlie changes in infant stress responses. It has been suggested that maternal glucocorticoids may mediate this epigenetic effect. We examined this hypothesis by determining the impact of maternal cortisol and depressive symptoms during pregnancy on infant NR3C1 and BDNF DNA methylation. Fifty-seven pregnant women were recruited during the second or third trimester. Participants self-reported depressive symptoms and salivary cortisol samples were collected diurnally and in response to a stressor. Buccal swabs for DNA extraction and DNA methylation analysis were collected from each infant at 2 months of age, and mothers were assessed for postnatal depressive symptoms. Prenatal depressive symptoms significantly predicted increased NR3C1 1F DNA methylation in male infants (ß = 2.147, P = 0.044). Prenatal depressive symptoms also significantly predicted decreased BDNF IV DNA methylation in both male and female infants (ß = -3.244, P = 0.013). No measure of maternal cortisol during pregnancy predicted infant NR3C1 1F or BDNF promoter IV DNA methylation. Our findings highlight the susceptibility of males to changes in NR3C1 DNA methylation and present novel evidence for altered BDNF IV DNA methylation in response to maternal depression during pregnancy. The lack of association between maternal cortisol and infant DNA methylation suggests that effects of maternal depression may not be mediated directly by glucocorticoids. Future studies should consider other potential mediating mechanisms in the link between maternal mood and infant outcomes.

Paternal influences on offspring development: behavioural and epigenetic pathways.

Although mammalian parent-offspring interactions during early life are primarily through the mother, there is increasing evidence for the impact of fathers on offspring development. A critical issue concerns the pathways through which this paternal influence is achieved. In the present review, we highlight the literature suggesting several of these routes of paternal effects in mammals. First, similar to mothers, fathers can influence offspring development through the direct care of offspring, as has been observed in biparental species. Second, there is growing evidence that, even in the absence of contact with offspring, fathers can transmit environmentally-induced effects (i.e. behavioural, neurobiological and metabolic phenotypes induced by stress, nutrition and toxins) to offspring and it has been speculated that these effects are achieved through inherited epigenetic variation within the patriline. Third, fathers may also impact the quality of mother-infant interactions and thus achieve an indirect influence on offspring. Importantly, these pathways of paternal influence are not mutually exclusive but rather serve as an illustration of the complex mechanisms through which parental influence is achieved. These influences may serve to transmit traits across generations, thus leading to a transgenerational transmission of neurobiological and behavioural phenotypes.

Variation in maternal and anxiety-like behavior associated with discrete patterns of oxytocin and vasopressin 1a receptor density in the lateral septum.

The relationship between anxiety and maternal behavior has been explored across species using a variety of approaches, yet there is no clear consensus on the nature or direction of this relationship. In the current study, we have assessed stable individual differences in anxiety-like behavior in a large cohort (n=57) of female F2 hybrid mice. Using open-field behavior as a continuous and categorical (high vs. low) measure we examined the relationship between the anxiety-like behavior of virgin F2 females and the subsequent maternal behavior of these females. In addition, we quantified oxytocin (OTR) and vasopressin (V1a) receptor density within the lateral septum to determine the possible correlation with anxiety-like and maternal behavior. We find that, though activity levels within the open-field do predict latency to engage in pup retrieval, anxiety-like measures on this test are otherwise not associated with subsequent maternal behavior. OTR density in the dorsal lateral septum was found to be negatively correlated with activity levels in the open-field and positively correlated with frequency of nursing behavior. V1a receptor density was significantly correlated with postpartum licking/grooming of pups. Though we do not find support for the hypothesis that individual differences in trait anxiety predict variation in maternal behavior, we do find evidence for the role of OTR and V1a receptors in predicting maternal behavior in mice and suggest possible methodological issues (such as distinguishing between trait and state anxiety) that will be a critical consideration for subsequent studies of the anxiety-maternal behavior relationship. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

[PMTCT in Benin: Is the pregnant women's consent free and informed?] / Prévention de la transmission mère-enfant du VIH/sida au Bénin: le consentement des femmes au dépistage est-il libre et éclairé ?

INTRODUCTION: In international and national HIV/AIDS policies, free and informed consent is recognized as one of the major components of testing programs. For pregnant women, free and informed consent means that they should get information on prevention of mother-to-child transmission (PMTCT), understand them and make an independent choice after weighing the risks and advantages. However, no PMTCT program looked into the issue of consent. The objective of this paper is to explore the free and informed nature of pregnant women's consent with regard to testing and their rationale for accepting to be tested. METHODS: We used data collected within the framework of the analysis of the creation of the PMTCT program in Benin. This analysis is based on multiple case studies that covered six maternity homes selected from 56 operational sites. For the specific analysis of consent, we used both survey data and qualitative research data. FINDINGS: Apart from three cases of secret testing, the free nature of the consent to the test is respected on the PMTCT sites. Twenty-nine cases of refusal were recorded. The reasons put forth by most pregnant women include the fear of a positive test and its consequences on family life in 55.2% of cases and the expectation of their husbands' agreement or disagreement in 27.6% of cases. On the whole, the consent was free on all the sites but its informed nature is less respected.

Social influences on neurobiology and behavior: epigenetic effects during development.

The quality of the social environment can have profound influences on the development and activity of neural systems with implications for numerous behavioral and physiological responses, including the expression of emotionality. Though social experiences occurring early in development may be particularly influential on the developing brain, there is continued plasticity within these neural circuits amongst juveniles and into early adulthood. In this review, we explore the evidence derived from studies in rodents which illustrates the social modulation during development of neural systems, with a particular emphasis on those systems in which a long-term effect is observed. One possible explanation for the persistence of dynamic changes in these systems in response to the environment is the involvement of epigenetic mechanisms, and here we discuss recent studies which support the role of these mechanisms in mediating the link between social experiences, gene expression, neurobiological changes, and behavioral variation. This literature raises critical questions about the interaction between neural systems, the concordance between neural and behavioral changes, sexual dimorphism in effects, the importance of considering individual differences in response to the social environment, and the potential of an epigenetic perspective in advancing our understanding of the pathways leading to variations in mental health.

Patient safety and systematic reviews: finding papers indexed in MEDLINE, EMBASE and CINAHL.

OBJECTIVE: To develop search strategies for identifying papers on patient safety in MEDLINE, EMBASE and CINAHL. METHODS: Six journals were electronically searched for papers on patient safety published between 2000 and 2006. Identified papers were divided into two gold standards: one to build and the other to validate the search strategies. Candidate terms for strategy construction were identified using a word frequency analysis of titles, abstracts and keywords used to index the papers in the databases. Searches were run for each one of the selected terms independently in every database. Sensitivity, precision and specificity were calculated for each candidate term. Terms with sensitivity greater than 10% were combined to form the final strategies. The search strategies developed were run against the validation gold standard to assess their performance. A final step in the validation process was to compare the performance of each strategy to those of other strategies found in the literature. RESULTS: We developed strategies for all three databases that were highly sensitive (range 95%-100%), precise (range 40%-60%) and balanced (the product of sensitivity and precision being in the range of 30%-40%). The strategies were very specific and outperformed those found in the literature. CONCLUSION: The strategies we developed can meet the needs of users aiming to maximise either sensitivity or precision, or seeking a reasonable compromise between sensitivity and precision, when searching for papers on patient safety in MEDLINE, EMBASE or CINAHL.

Developmental shifts in the behavioral phenotypes of inbred mice: the role of postnatal and juvenile social experiences.

The interaction between genotype and environment is an important feature of the process of development. We investigate this interaction by examining the influence of postnatal cross-fostering and post-weaning cross-housing on the behavioral development of 129S and B6 mice. Following cross-fostering, we found significant alterations in the frequency of maternal care as a function of maternal strain and pup type as well as interactions between these variables. In adulthood, we find there are sex-specific and strain-specific alterations in anxiety-like behavior as a function of rearing environment, with males exhibiting more pronounced rearing-induced effects. Mixed-strain housing of weanlings was found to lead to alterations in home-cage social and feeding behavior as well as changes in adult anxiety-like responses of 129S mice. Anxiety-like behavior in B6 mice was altered as a function of the interaction between housing condition and weaning weight. These data illustrate the complex pathways through which early and later social experiences may lead to variations in behavior.

Epigenetic programming of phenotypic variations in reproductive strategies in the rat through maternal care.

Studies across multiple organisms reveal considerable phenotypic variation in reproductive tactics. In some species, this variation is associated with maternal effects in which variation in maternal investment results in stable individual differences in reproductive function. Recent studies with the rat suggest that maternal effects can alter the function of neuroendocrine systems associated with female sexual behaviour as well as maternal behaviour. These maternal effects appear to be mediated by epigenetic modifications at the promoter for oestrogen receptor alpha (ERalpha) and subsequent effects on gene expression. The tissue-specific nature of such effects may underlie the co-ordinated variation in multiple forms of reproductive function, resulting in distinct reproductive strategies.

A performance assessment framework for hospitals: the WHO regional office for Europe PATH project.

OBJECTIVE: The World Health Organization (WHO) Regional Office for Europe launched in 2003 a project aiming to develop and disseminate a flexible and comprehensive tool for the assessment of hospital performance and referred to as the performance assessment tool for quality improvement in hospitals (PATH). This project aims at supporting hospitals in assessing their performance, questioning their own results, and translating them into actions for improvement, by providing hospitals with tools for performance assessment and by enabling collegial support and networking among participating hospitals. METHODS: PATH was developed through a series of four workshops gathering experts representing most valuable experiences on hospital performance assessment worldwide. An extensive review of the literature on hospital performance projects was carried out, more than 100 performance indicators were scrutinized, and a survey was carried out in 20 European countries. RESULTS: Six dimensions were identified for assessing hospital performance: clinical effectiveness, safety, patient centredness, production efficiency, staff orientation and responsive governance. The following outcomes were achieved: (i) definition of the concepts and identification of key dimensions of hospital performance; (ii) design of the architecture of PATH to enhance evidence-based management and quality improvement through performance assessment; (iii) selection of a core and a tailored set of performance indicators with detailed operational definitions; (iv) identification of trade-offs between indicators; (v) elaboration of descriptive sheets for each indicator to support hospitals in interpreting their results; (vi) design of a balanced dashboard; and (vii) strategies for implementation of the PATH framework. CONCLUSION: PATH is currently being pilot implemented in eight countries to refine its framework before further expansion.

[Migration, ethics and public health in Quebec]. / Migration, éthique et santé publique au Québec.

This article analyses the ethical issues of migration in relation to public health in Quebec. There are two objectives: to describe the progression of analysis of the migration phenomenon in public health over the last thirty years and to state the ethical debate it raises. The progression of analysis of the migration phenomenon has been characterised by various approaches: intercultural, acculturation, transcultural, and migratory journey. Although these approaches have contributed to the development of knowledge about the reality of immigration, they have also, in spite of themselves, generated stigmatisation, discrimination and the proliferation of prejudices. Generally, findings that have emerged when migration is taken into account indicate an imbalance of power. For some, to focus on the phenomenon of migration promotes the power imbalance while for others, to disregard it masks the issue.

Effect of age on the conformity rate to short-acting beta-agonist use criteria in asthma.

STUDY OBJECTIVES: Assess compliance to asthma guidelines and influence of age concerning inhaled short-acting beta2-agonist (SABA) utilization in 5 to 45-year-old asthmatic subjects in the province of Quebec. DESIGN: Population-based retrospective drug utilization review using a computerized database of claims submitted to a private prescription drug insurance plan. PATIENTS: Subjects who received at least one outpatient prescription of SABA (age range, 5 to 45 years) for the treatment of asthma between January 1996 and December 1997. MEASUREMENTS: Percentages of patients whose use was appropriate according to the criteria regarding the average daily dose of SABA. Use was considered appropriate if the consumption rate corresponded to a maximum of two puffs per day (Salbutamol equivalent) in subjects who did or did not use inhaled corticosteroids (ICS) at an estimated maximum dose of 800 mcg/day of Beclomethasone (BDP) equivalent for the 5 to 11-year-olds and 1000 mcg/day for the 12 to 45-year-olds. RESULTS: In 1996, use was found to be appropriate for 74.4% of the 394 patients who received an SABA without ICS as compared with 70.7% for 593 patients in 1997. If we consider those who received an ICS at low to moderate doses, appropriate use was found for 51% of the 375 patients in 1996 and 57.6% for 254 patients in 1997. If we exclude patients who did not renew their SABA, appropriate use drops to 46.3% for 1996 and 34.3% for 1997 for the group who receive SABA without ICS (29.4% and 37.6%, respectively, for those with ICS). There is a relationship between age and appropriateness; the percentage of appropriateness was higher for the younger ones (5 to 14-year-old group; 83% in 1996 and 86% in 1997 for the patients who received a SABA without IS and 58.5% in 1996 and 73% in 1997 for the patients who received a SABA using ICS (p < 0.05). CONCLUSION: Our results indicate that adherence to asthma guidelines concerning SABA is poor. SABA are still overused, particularly among ICS users, which might be explained by undertreatment or poor compliance. Appropriate SABA use was significantly more common among younger groups (p < 0.05). This can be explained by better treatment in that age group, better compliance or less severe asthma.

Cost-benefit and cost-effectiveness analysis of a disability prevention model for back pain management: a six year follow up study.

AIMS: To test the long term cost-benefit and cost-effectiveness of the Sherbrooke model of management of subacute occupational back pain, combining an occupational and a clinical rehabilitation intervention. METHODS: A randomised trial design with four arms was used: standard care, occupational arm, clinical arm, and Sherbrooke model arm (combined occupational and clinical interventions). From the Quebec WCB perspective, a cost-benefit (amount of consequence of disease costs saved) and cost-effectiveness analysis (amount of dollars spent for each saved day on full benefits) were calculated for each experimental arm of the study, compared to standard care. RESULTS: At the mean follow up of 6.4 years, all experimental study arms showed a trend towards cost benefit and cost effectiveness. These results were owing to a small number of very costly cases. The largest number of days saved from benefits was in the Sherbrooke model arm. CONCLUSIONS: A fully integrated disability prevention model for occupational back pain appeared to be cost beneficial for the workers' compensation board and to save more days on benefits than usual care or partial interventions. A limited number of cases were responsible for most of the long term disability costs, in accordance with occupational back pain epidemiology. However, further studies with larger samples will be necessary to confirm these results.

Waiting time for rehabilitation services for children with physical disabilities.

BACKGROUND: Early rehabilitation may minimize disability and complications. However, children often wait a long time to gain admission to rehabilitation centres. OBJECTIVES: To describe waiting times for paediatric physical and occupational therapy and to determine factors associated with these waiting times. RESEARCH DESIGN: The study was a prospective cohort design. Patients were followed from 1 January 1999 to 1 March 2000. SUBJECTS: All children with physical disabilities, aged 0-18 years, referred in 1999 from the Montreal Children's Hospital to paediatric rehabilitation centres. MEASURES: Data on date of referral, date of first appointment at the rehabilitation centre, age, gender, diagnosis, region and language were obtained from the rehabilitation transfer database. Primary family caregivers of children who were transferred to a rehabilitation facility participated in a telephone interview regarding their perceptions of the transfer process. RESULTS: There were 172 children referred to rehabilitation facilities. The mean age of the children was 2.5 years. Average waiting time was 157.4 days (SD 57.1) for occupational therapy and 129.4 days (SD 51.6) for physical therapy. Decreased waiting time was associated with living in the city as opposed to the suburbs (hazard ratio=1.77; 95% confidence interval=0.92-3.41) and inversely associated with age (hazard ratio=0.46; 95% confidence interval=0.34-0.62). Among the 41 primary family caregivers who participated in the survey, higher empowerment scores were associated with shorter waits for rehabilitation. CONCLUSION: Waiting time for rehabilitation services needs to be reduced. Empowered parents appear to manoeuvre within the system to reduce waiting times for their children.

Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors.

Naturally occurring variations in maternal licking/grooming influence neural development and are transmitted from mother to female offspring. We found that the induction of maternal behavior in virgin females through constant exposure to pups (pup sensitization) was significantly shorter in the offspring of High compared with Low licking/grooming mothers, suggesting differences in maternal responsivity. In randomly selected females screened for individual differences in maternal responsivity and subsequently mated, there was a significant and negative correlation (r = -0.73) between the latency to exhibit maternal behavior in the pup sensitization paradigm and the frequency of pup licking/grooming during lactation. Females that were more maternally responsive to pups and that showed increased levels of pup licking/grooming also showed significantly higher oxytocin receptor levels in the medial preoptic area, the lateral septum, the central nucleus (n.) of the amygdala, the paraventricular n. of the hypothalamus, and the bed n. of the stria terminalis. Intracerebroventricular administration of an oxytocin receptor antagonist to mothers on postpartum day 3 completely eliminated the differences in pup licking/grooming, suggesting that differences in oxytocin receptor levels are functionally related to maternal behavior. Finally, estrogen treatment of virgin females significantly increased oxytocin receptor binding in the medial preoptic area and lateral septum of female offspring of High, but not Low, licking/grooming mothers. These findings suggest that maternal licking/grooming influences the development of estrogen sensitivity in brain regions that regulate maternal behavior, providing a potential mechanism for the intergenerational transmission of individual differences in maternal behavior.