The effects of diazepam on fear extinction in nulliparous and primiparous female rats.

Benzodiazepines undermine the success of exposure therapy in humans with anxiety disorders, and impair the long-term memory of fear extinction (the laboratory basis of exposure therapy) in rodents. However, most rodent studies on fear extinction and benzodiazepines have been conducted in male rodents. In female rodents, the estrous cycle influences the consolidation of fear extinction memories and sensitivity to benzodiazepines. In addition, pregnancy leads to long-term changes in the neurobiological, hormonal, and behavioural features of fear extinction, as well as the responsivity to benzodiazepines. Therefore, the present experiments examined the impact of benzodiazepines on fear extinction in female rats with and without reproductive experience. Age-matched nulliparous (no reproductive experience) and primiparous (one prior reproductive experience; tested one-month post-weaning) rats received fear conditioning to a discrete cue. The next day, rats were administered the benzodiazepine diazepam (2 mg/kg, s.c), or vehicle, prior to or immediately after extinction training. Rats were then tested the next day, drug free, for extinction retention. Similar to previous findings in males, diazepam impaired extinction retention in both nulliparous and primiparous rats when administered either pre- or post-extinction training. These findings may have potential clinical implications as they suggest that benzodiazepine use in conjunction with exposure therapy may undermine long-term treatment success in women with and without reproductive experience, although this remains to be tested in human populations. Moreover, these findings are theoretically important when considered in light of previous studies showing dissociable mechanisms of fear extinction in females pre- versus post-pregnancy.

The behavioral neuroendocrinology of maternal behavior: Past accomplishments and future directions.

Research on the neuroendocrine-endocrine-neural regulation of maternal behavior has made significant progress the past 50 years. In this mini-review progress during this period has been divided into five stages. These stages consist of advances in the identification of endocrine factors that mediate maternal care, the characterization of the neural basis of maternal behavior with reference to endocrine actions, the impact of developmental and experiential states on maternal care, the dynamic neuroplastic maternal brain, and genes and motherhood. A final section concludes with a discussion of future directions in the field of the neurobiology/neuroendocrinology of motherhood.

d-Cycloserine and estradiol enhance fear extinction in nulliparous but not primiparous female rats.

Female reproductive experience has been shown to alter the hormonal, neurobiological and behavioural features of fear extinction, which is the laboratory basis of exposure therapy. This raises uncertainties as to whether pharmacological agents that enhance fear extinction in reproductively inexperienced females are equally effective in reproductively experienced females. The aim of the current study was therefore to compare the effects of two pharmacological enhancers of fear extinction, d-cycloserine (DCS) and estradiol, between nulliparous (virgin) and primiparous (reproductively experienced) female rats. In Experiment 1, nulliparous and primiparous females received systemic administration of either DCS or saline immediately after extinction training, and were tested for extinction recall the following day. DCS enhanced extinction recall in nulliparous females that showed low levels of freezing at the end of extinction training, but not among those that showed high levels of freezing at the end of extinction training. DCS did not enhance fear extinction in primiparous females, regardless of their level of freezing at the end of extinction training. In Experiment 2, nulliparous and primiparous female rats received systemic administration of either estradiol or vehicle prior to extinction training. Estradiol enhanced extinction recall among nulliparous females, but not primiparous females. Increasing the dose of estradiol administered prior to extinction training did not alter the outcomes in primiparous females (Experiment 3). Together, these findings suggest that reproductive status may be an important individual difference factor associated with the response to pharmacological modulators of extinction in rats. The implications of these findings for the pharmacological augmentation of exposure therapy in clinical populations are discussed.

Transient and persistent behavioral and molecular changes in primiparous female Wistar rats.

Motherhood brings about a multitude of behavioral and physiological changes in dams and some of these persist until after weaning. We studied behavioral changes associated with reproductive experience at lactating day (LD)8, at weaning (LD21), and 28 days post-weaning (PW28) compared to nulliparous (NP) females. Furthermore, in another cohort of animals, we quantified mRNA expression of five target genes known to be associated with maternal experience: arginin-vasopressin(Avp) and its 1A receptor(Avpr1a), oxytocin(Oxt) and its receptor(Oxtr), and corticotropin-releasing hormone(Crh) in three key maternal region: the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST) and paraventricular hypothalamic nucleus(PVN). Although dams were slightly less anxious than NP at LD8, this effect did not persist at LD21 and PW28. No differences in social preference were found between the four groups. In the maternal responsiveness test (MRT), LD8 and LD21 dams were immediately responsive to pups whereas NP largely avoided the pups throughout 12-day period. PW28 females were significantly more responsive to pups than NP females, but less than LD8 and LD21 females. The mRNA expression of Avp in the PVN, Avpr1a in the BNST and Oxtr in the MPOA and BNST was increased, whereas mRNA expression of Avpr1a was reduced in the PVN, at LD8 compared to NP. Although Oxtr in the BNST and Avp in the PVN were still somewhat (non-significantly) increased at LD21, all levels of gene expression had normalized at PW28. Our results emphasize the transient nature of these behavioral and molecular adaptations, except for a persistent up-regulation of maternal responsiveness.

Long-term alterations in neural and endocrine processes induced by motherhood in mammals.

This article is part of a Special Issue "Parental Care". The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female's biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages.

Relationship between prolactin, reproductive experience, and parental care in a biparental songbird, the zebra finch (Taeniopygia guttata).

Hormonal systems have long been thought to play an important role in stimulating the onset of parental behavior, a critical component of reproductive success in a variety of taxa. Elevations in the peptide hormone prolactin (PRL) have been repeatedly positively correlated with the onset and maintenance of parental care across vertebrate species. A causal role for PRL in parental care has been established in several mammalian species, but less evidence for a causal role of PRL and parental care exists in birds. The zebra finch, a socially monogamous, biparental songbird, is an exceptionally useful animal model to study parental care and other close social relationships. Both sexes share parental care equally, exhibit the same parental behaviors, and show a marked improvement in breeding success with experience. We hypothesize that PRL is critically involved in the expression of zebra finch parental care and predict that circulating PRL levels will increase with breeding experience. To begin testing this, we measured plasma PRL concentrations in 14 male-female zebra finch pairs (N=28) across two breeding cycles, using a repeated measures design. PRL was measured in the birds' first, reproductively inexperienced, breeding cycle beginning at courtship and extending through chick fledging. PRL was measured again during the birds' second, reproductively experienced, breeding cycle, beginning with egg laying until chick fledging. We found that plasma PRL is significantly elevated from non-breeding concentrations during late incubation and early post-hatch care and that this elevation is greater in the reproductively experienced cycle compared to the inexperienced cycle. Findings of this study will be used to inform hypotheses and predictions for future experimental manipulations of PRL during parental care.

Hippocampal learning, memory, and neurogenesis: Effects of sex and estrogens across the lifespan in adults.

This article is part of a Special Issue "Estradiol and Cognition". There are sex differences in hippocampus-dependent cognition and neurogenesis suggesting that sex hormones are involved. Estrogens modulate certain forms of spatial and contextual memory and neurogenesis in the adult female rodent, and to a lesser extent male, hippocampus. This review focuses on the effects of sex and estrogens on hippocampal learning, memory, and neurogenesis in the young and aged adult rodent. We discuss how factors such as the type of estrogen, duration and dose of treatment, timing of treatment, and type of memory influence the effects of estrogens on cognition and neurogenesis. We also address how reproductive experience (pregnancy and mothering) and aging interact with estrogens to modulate hippocampal cognition and neurogenesis in females. Given the evidence that adult hippocampal neurogenesis plays a role in long-term spatial memory and pattern separation, we also discuss the functional implications of regulating neurogenesis in the hippocampus.

Walking for Cognitive Health: Previous Parity Moderates the Relationship Between Self-Reported Walking and Cognition.

BACKGROUND: Older females show greater cognitive gains from physical activity (PA) than males, which may be related to long-term consequences of female-specific reproductive events (eg, pregnancy) on cognitive health. METHODS: To determine whether previous parity could moderate the relationship between PA and cognitive decline in older women, we conducted secondary analyses of data from the Health, Aging, and Body Composition Study. We tested whether the association between average PA over 10 years and cognition (Modified Mini-Mental State Examination [3MS]) and executive functioning (digit symbol substitution test [DSST]) over 10 years varied by previous parity (nulliparity, low parity, medium parity, and grand multiparity). An analysis of covariance was performed with cognition (average and change over 10 years) as the dependent variables, parity as a categorical predictor, average PA as a continuous predictor, and a set of relevant covariates. RESULTS: Significant interactions were found between PA and parity group for all 4 comparisons: average 3MS (p = .014), average DSST (p = .032), change in 3MS (p = .016), and change in DSST (p = .017). Simple slope analyses indicated the positive relationship between PA and average 3MS and DSST was only significant in the nulliparity and grand multiparity groups, and the positive relationship between PA and change in 3MS and DSST was only significant in the grand multiparity group. CONCLUSION: The findings suggest the relationship between self-reported walking and cognitive performance was strongest in the groups at risk for cognitive decline and dementia, the nulliparous and grand multiparous groups.

Beyond sex differences: short- and long-term effects of pregnancy on the brain.

Growing attention has been directed to the inclusion of females in neuroscience studies, and to the importance of studying sex as a biological variable. However, how female-specific factors such as menopause and pregnancy, affect the brain remains understudied. In this review, we use pregnancy as a case in point of a female-unique experience that can alter neuroplasticity, neuroinflammation, and cognition. We examine studies in both humans and rodents indicating that pregnancy can modify neural function in the short term, as well as alter the trajectory of brain aging. Furthermore, we discuss the influence of maternal age, fetal sex, number of pregnancies, and presence of pregnancy complications on brain health outcomes. We conclude by encouraging the scientific community to prioritize researching female health by recognizing and including factors such as pregnancy history in research.

Reproductive experiences and factors influencing contraceptive use among female head-porters in Ghana: A cross-sectional study.

Background and Aims: Female head-porters are a cohort of women who have migrated from their rural communities into commercial cities in search of better economic opportunities. These young women are vulnerable to untoward reproductive experiences. The study assesses the reproductive experiences of women and the factors influencing contraceptive use among them. Methods: A cross-sectional study was conducted from January to May 2021 in the Kumasi Metropolis (n = 280). The study included 280 female head-porters within the reproductive age of 15-49 years. Convenience sampling and consecutive recruitment were used to obtain the needed sample size. All statistical significance was declared at a p-value of <0.05. Results: Forty-two percent of respondents had a history of contraceptive use (all modern or artificial contraception). The study found gravidity (p < 0.0001), parity (p < 0.0001), number of sexual partners post-migration (p = 0.008), and age of first sex (p = 0.033) to be associated with contraceptive use among female head-porters. Conclusion: Fourteen percent had experienced sexual exploitation post-migration, the first sexual encounter of one-third of participants were nonconsensual, 19% had sex at or before 16 years, and 72% were aware of contraception. Reproductive experiences such as gravidity and sexual debut (age at first sex) have a significant influence on the use of contraception.