Article

Spatial Working Memory and Hippocampal Size across Pregnancy in Rats

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Abstract

The present experiments investigated the effects of pregnancy on performance in the Morris water maze and on hippocampal volume. In the first study, pregnant rats (in between the first and second trimester) outperformed nonpregnant rats on the Morris water maze on 1 day of testing. In the second study, rats were tested in a working memory variation of the maze in which the spatial location of the platform varied. Pregnant females traveled shorter distances than nonpregnant females during the first two trimesters, but performed worse than nonpregnant females during the third trimester. Latency measures showed a similar profile. Group differences in performance were not related to changes in swim speed. However, changes in performance in pregnant females may be related to estrogen, progesterone, and/or corticosterone levels during pregnancy, with low levels of estradiol and high levels of progesterone being associated with better performance. There were no significant differences between pregnant and nonpregnant animals on any of the brain measures, although pregnant animals tended to have a smaller hippocampus than nonpregnant animals. These results indicate that pregnancy can affect performance, possibly related to the hormonal changes that accompany pregnancy.

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... In a subsequent study, adult hippocampal neurogenesis in postmortem human brains persisted into the eighth decade of life (Boldrini et al., 2018 (Cuttler, Graf, Pawluski, & Galea, 2011). Late pregnant rats (GD 21) are also impaired in the Morris water maze, a spatial-memory task, compared with non-pregnant rats (Galea et al., 2000). New hippocampal neurons are activated in spatial learning and memory task in males (reviewed in Epp, Chow, & Galea, 2013) and severe losses of proliferating and immature neurons in the hippocampus significantly impaired memory function (Winocur, Wojtowicz, Sekeres, Snyder, & Wang, 2006). ...
... New hippocampal neurons are activated in spatial learning and memory task in males (reviewed in Epp, Chow, & Galea, 2013) and severe losses of proliferating and immature neurons in the hippocampus significantly impaired memory function (Winocur, Wojtowicz, Sekeres, Snyder, & Wang, 2006). However, hippocampal volume (and volumes of regions within the hippocampus) did not differ between pregnant and non-pregnant rats (Galea et al., 2000). Therefore, more work is needed to determine the mechanisms of pregnancy-associated cognitive impairments and species-specific differences in hippocampal neurogenesis across reproductive events. ...
... During early postpartum, rats with neonates must remain close to the nest for frequent feeding, potentially minimizing the demand for maintaining spatial navigation-related hippocampal processes. Indeed, late pregnant and early postpartum rats are impaired in the Morris water maze, a hippocampus-dependent spatial learning task (Darnaudery et al., 2007;Galea et al., 2000). Thus, decreased hippocampal neurogenesis and transient reduction in spatial cognitive abilities during the postpartum period might maximize reproductive fitness. ...
... However, there were no delays placed between the information trial (trial 1) and the retention trials (trials 2, 3, 4), a typical feature for evaluating working memory performance (Steele and Morris, 1999). Endogenous estrogen failed to improve working memory performance during pregnancy in rats, as measured in the water maze (Galea et al., 2000). Pregnant females in their first and second trimesters, when estrogen levels are low (~ 15 pg/ml) and progesterone levels are high, outperformed pregnant females in their third trimester and nonpregnant females with high estrogen titers (~'40 pg/ml) but low progesterone levels. ...
... In addition, the ratio of estrogen to progesterone may be an important factor. Rats in their first and second trimesters of pregnancy, when low estradiol combines with high progesterone, performed better on place learning trials than nonpregnant females, whereas females in their third trimester of pregnancy, when high estradiol combines with low progesterone, performed worse than nonpregnant females (Galea et al., 2000). Although the task used in this study was intended as a measure of working memory performance, features such as a stationary platform throughout each trimester, suggest that the procedure measured reference memory performance according to its traditional definition (Section IICla). ...
... A second technique has been to use computerized tracking to assess not only the swimming latency but also the swimming distance to escape to a hidden platform, providing a measure of swim speed that reflects the quality of motor function in treated and control animals. Most water maze studies have not found changes in swim speed that could account for the effects of estrogen and progesterone on reference memory performannce (Chesler and Juraska, 2000;Galea et al., 1995Galea et al., , 2000Juraska, 1997, 2000), except for a report in which ovariectomized gerbils treated with Silastic capsules of estradiol had increased escape latencies that could be accounted for by decreased swim speed (Kondo et al., 1997). ...
Article
Although the roles of estrogen, progesterone, and testosterone in the activation and maintenance of re-productive function are well established, emerging ev-idence indicates that these same steroids influence per-formance on measures of learning and memory in various species, including humans. These effects are complex and vary with task, gender, and age, as well as the regimens of steroid exposure. Gonadal steroids can affect performance on appetitive and aversive tasks; spatial and nonspatial tasks; conditioning; and acqui-sition, consolidation, and retention. However, the ef-fects of steroids on learning and memory often are moderate in magnitude and can improve, impair, or not affect performance on various measures of learn-ing and memory. Consequently, the biological and be-havioral significance of steroid modulation of cogni-tive performance remains to be determined. A more important action of gonadal steroids may prove to be their ability to assist neurons in confronting risks en-countered thoughout life. These neuroprotective ac-tions could have profound consequences for the pre-vention and treatment of diseases of aging, including Alzheimer's disease and other well-known pathologies. A better understanding of the mechanisms of steroid action and cognitive function should lead to the devel-opment of new steroid treatments to improve neuronal function that has been compromised by trauma, age, or disease.
... Impairments in cognition during pregnancy are dependent on a number of factors, including trimester, fetal sex, and parity. The third trimester of pregnancy and the early postpartum period in particular are associated with verbal and spatial memory impairments relative to the first two trimesters of pregnancy (Darnaudery et al., 2007;Galea et al., 2000;Glynn, 2012). For example, in rodents, spatial ability is impaired during the third week of pregnancy (Galea et al., 2000;Keenan et al., 1998), while in women, verbal memory and processing speed are impaired in the third but not first two trimesters (Keenan et al., 1998;Christensen et al., 2010). ...
... The third trimester of pregnancy and the early postpartum period in particular are associated with verbal and spatial memory impairments relative to the first two trimesters of pregnancy (Darnaudery et al., 2007;Galea et al., 2000;Glynn, 2012). For example, in rodents, spatial ability is impaired during the third week of pregnancy (Galea et al., 2000;Keenan et al., 1998), while in women, verbal memory and processing speed are impaired in the third but not first two trimesters (Keenan et al., 1998;Christensen et al., 2010). Fetal sex alters cognition during pregnancy as women pregnant with girls perform more poorly than women pregnant with boys on working memory and spatial (mental rotation) tasks throughout gestation and into the postpartum period (Vanston and Watson, 2005). ...
... Animal studies mirror findings in women, showing that the third week of gestation in rodents is associated with impairments in spatial ability (Darnaudery et al., 2007;Galea et al., 2000). However, it is important to note that there are differences in pregnancy hormone profiles in rat versus human (Brett and Baxendale, 2001;Galea et al., 2000;Pawluski et al., 2009). ...
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Reproductive experience (pregnancy and mothering) affects both hippocampus-dependent learning and memory and neurogenesis in the mother during the postpartum period and long after weaning. However, what is less known is that reproductive experience is associated with an increased risk to develop Alzheimer's pathology and disease. There are only a handful of studies that have examined the maternal brain into older age. This review will outline the short- and long-term effects of reproductive experience on the female brain with respect to cognition and implications for increased risk to develop neurodegenerative disorders in the long term with motherhood. The neuroendocrine correlates are discussed, with a focus on the hippocampus and ovarian hormones, and integrating human observational studies with experimental animal models.
... In laboratory rodents, cognitive performance, using spatial hippocampus-dependent tasks, fluctuates during pregnancy and the postpartum period (reviewed in Roes and Galea, 2016;Workman et al., 2012). During early and mid-pregnancy, primiparous female rats display enhanced spatial performance compared to nulliparous females (Bodensteiner et al., 2006;Galea et al., 2000). In contrast, pregnant females late in gestation or primiparous females early in the postpartum display an impaired spatial performance compared to nulliparous females (Darnaudéry et al., 2007;Galea et al., 2000). ...
... During early and mid-pregnancy, primiparous female rats display enhanced spatial performance compared to nulliparous females (Bodensteiner et al., 2006;Galea et al., 2000). In contrast, pregnant females late in gestation or primiparous females early in the postpartum display an impaired spatial performance compared to nulliparous females (Darnaudéry et al., 2007;Galea et al., 2000). Intriguingly, after weaning, there is another shift in performance ability with primiparous rats displaying better working and reference memory than nulliparous rats (Kinsley et al., 1999;Pawluski et al., 2006aPawluski et al., , 2006b. ...
... Animal studies have also found brain plasticity changes during pregnancy and the postpartum period. Pregnant rats have slightly smaller hippocampi (Galea et al., 2000) but greater cortical thickness (Hamilton et al., 1977) compared to non-pregnant rats. In the midpostpartum, primiparous female rats have lower brain weight and hippocampal volume compared to nulliparous females (Hillerer et al., 2014). ...
... These changes promote neuronal and glial remodeling that is critical for cognition, learning, and memory. For example, spatial working memory varies during rat pregnancy, and the memory retention enhanced by E2 is maintained by P4 (45,46). Further data show that E2 and P4 modify neuronal morphology of the hippocampus of rats and monkeys, an important region for memory consolidation (47,48). ...
... During pregnancy, circulating sex hormones are increased in the rat; E2 levels are two-fold and P4 three-fold higher compared with the hormone levels during proestrus day (131,132). The brain displays diverse morphophysiological changes during pregnancy including cell plasticity (36,45,133). Furthermore, in the medial preoptic area (POA), late pregnant rats have bigger neuronal somata than ovariectomized rats (134), suggesting that E2 and P4 play an important role in neuronal morphology. ...
Article
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In the brain of female mammals, including humans, a number of physiological and behavioral changes occur as a result of sex hormone exposure. Estradiol and progesterone regulate several brain functions, including learning and memory. Sex hormones contribute to shape the central nervous system by modulating the formation and turnover of the interconnections between neurons as well as controlling the function of glial cells. The dynamics of neuron and glial cells morphology depends on the cytoskeleton and its associated proteins. Cytoskeletal proteins are necessary to form neuronal dendrites and dendritic spines, as well as to regulate the diverse functions in astrocytes. The expression pattern of proteins, such as actin, microtubule-associated protein 2, Tau, and glial fibrillary acidic protein, changes in a tissue-specific manner in the brain, particularly when variations in sex hormone levels occur during the estrous or menstrual cycles or pregnancy. Here, we review the changes in structure and organization of neurons and glial cells that require the participation of cytoskeletal proteins whose expression and activity are regulated by estradiol and progesterone.
... Serum estradiol was assayed using a Coat-A-Count kit (Diagnostic Products Corporation, Los Angeles, CA) modified for low expected levels of estradiol. Previous studies from our laboratory found that the intra-assay coefficent is less than 5% (Ormerod & Galea, 2000). ...
... Recall that performance during acquisition in the present task does not appear to rely on the hippocampus (Lipska et al., 2002). Intriguingly, supraphysiological levels of estradiol (EB10) in the present study signficantly increased dentate gyrus volume consistent with previous studies in female meadow voles (Galea, Perrot-Sinal, Kavaliers & Ossenkopp, 1999) and in previous pregnant and lactating rats (Galea et al., 2000). ...
... In general, early-and mid-pregnancy (lower levels of estradiol) are associated with enhanced spatial performance, but the opposite is true during late pregnancy (higher levels of estradiol; Galea et al., 2000;Macbeth et al., 2008). Additionally, the early postpartum period is characterized by impaired hippocampus-dependent learning, while the late postpartum period and after weaning are characterized by enhanced hippocampus-dependent learning compared to non-parous rats (Darnaudéry et al., 2007;Kinsley et al., 1999;Gatewood et al., 2005;Kinsley et al., 2012). ...
... The brain changes drastically across pregnancy and the postpartum period. Hippocampal volume is significantly reduced in pregnant rats (Galea et al., 2000) and overall brain volume is reduced in humans but returns to pre-pregnancy level after parturition (Oatridge et al., 2002). In mice, BrdU-labeled cell survival is decreased during the second week of gestation but returns to nulliparous levels 21 days after parturition (Rolls et al., 2008). ...
Article
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. Copyright © 2015. Published by Elsevier Inc.
... Anecdotal reports of this "baby brain", "porridge brain", or "maternal amnesia" are substantiated, in part, with research findings of decreased verbal recall and prospective memory in women during late pregnancy and the early postpartum period, particularly when everyday life memory tests are used outside the laboratory (for further discussion see (Christensen et al., 2010;Crawley et al., 2003;Cuttler et al., 2011;de Groot et al., 2006;Parsons et al., 2004;Poser et al., 1986)). Rodent research has also shown that hippocampal-dependent spatial memory is impaired in the rat dam during late gestation and early postpartum period (Darnaudery et al., 2007;Galea et al., 2000). ...
... Interestingly ventricle size shows a concomitant increase during pregnancy, with a decrease during the postpartum period, demonstrating an overall decrease in brain volume in pregnant women (Oatridge et al., 2002). Recent work in rodents has reported a reduction of brain size during early lactation (Hillerer et al., 2014b) and a reduction in hippocampal volume in pregnant rats (Galea et al., 2000). ...
Article
It is becoming clear that the female brain has an inherent plasticity that is expressed during reproduction. The changes that occur benefit the offspring, which in turn secures the survival of the mother's genetic legacy. Thus, the onset of maternal motivation involves basic mechanisms from genetic expression profiles, to hormone release, to hormone-neuron interactions, all of which fundamentally change the neural architecture - and for a period of time that extends, interestingly, beyond the reproductive life of the female. Although multiple brain areas involved in maternal responses are discussed, this review focuses primarily on plasticity in the maternal hippocampus during pregnancy, the postpartum period and well into aging as it pertains to changes in cognition. In addition, the effects of prolonged and repeated stress on these dynamic responses are considered. The maternal brain is a marvel of directed change, extending into behaviors both obvious (infant-directed) and less obvious (predation, cognition). In sum, the far-reaching effects of reproduction on the female nervous system provide an opportunity to investigate neuroplasticity and behavioral flexibility in a natural mammalian model. Copyright © 2015. Published by Elsevier Inc.
... In addition to the brain areas related to maternal behavior, the maternal brain acquires great plasticity in areas related to emotion and cognition. Learning and memory may also be affected by pregnancy and/or maternal experience (Galea et al., 2000;Brett and Baxendale, 2001;Pawluski and Galea L a, 2007). In rodents, reproductive experience appears to have a beneficial impact on learning and memory both before and after weaning (Gatewood et al., 2005;Lemaire et al., 2006;Pawluski and Galea L a, 2007;Pawluski et al., 2016). ...
... In summary, the first RE is an event that faces the female with a new environment with numerous physical, metabolic and hormonal demands; in this context, the separation of pups results in a stressful experience which is detrimental to the memory and some maternal behaviors. Second-time mothers have an advantage in confronting this kind of socially stressful situation because experience has already produced changes and maternal behaviors are expressed more easily (Galea et al., 2000). Although multiparity attenuates some of the detrimental effects produced by the pup-separation stress, it is not enough to temper all the alterations, indicating that even in mothers with previous experience the contact with the offspring is of fundamental importance for the adequate behavioral, emotional and cognitive outcomes in dams. ...
Article
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Reproductive experience in mammals produces significant neuroendocrine and behavioral changes that are necessary to ensure the survival of the mother and the young. Exposure to stress during postpartum may affect the proper development of maternal behaviors. The present study examined whether previous reproductive experience affects neurobehavioral responses in females exposed to mother-infant separation stress during the postpartum period (4.5 h/day for 3 weeks). Anxiety-like behavior and spatial learning were evaluated in nulliparous (NP), primiparous (PRI) and multiparous (MULT). In maternal animals (PRI and MULT), maternal behavior was also assessed. Cell survival and proliferation in the dentate gyrus, as well as BDNF expression in the hippocampus, were evaluated by immunohistochemistry as possible candidates for mediating brain plasticity in response to reproductive experience and stress. Anxiety-like behavior as measured on the open field test showed an increase in NP and PRI-stressed, while neither stressed nor unstressed MULT expressed this behavior. Maternal unstressed animals both PRI and MULT exhibited enhanced memory task performance in the Barnes maze. Multiparity increased cell proliferation and cell survival in female rats and these changes occurred independently of pup exposure. The expression of BDNF was higher in the CA1 area in MULT rats. Although multiparity protects the mother against some of the effects of maternal separation stress, promoting behaviors directed to the pups during the early postpartum, preventing anxiety-like behaviors and mitigating memory deterioration after weaning, the data showed that disrupting natural dam-pup interaction produced neurobiological consequences on the mother even with multiple reproductive experience.
... Due to the aforementioned link between reproductive hormones and the hippocampus, this brain region is a promising mediator linking differences in reproductive hormones to risk of depression. For instance, in the peripartum period, alongside an increased risk of depression diagnosis and robust hormonal changes (Pařízek et al., 2014;Schock et al., 2016;Stuebe et al., 2015), there are observable alterations to hippocampal volume in rodents, which return to normal in the weeks following parturition (Galea et al., 2000). ...
... In the context of previous research, our findings support reports which have revealed an association between higher estradiol levels and smaller hippocampal volumes (Heijer et al., 2003;Seiger et al., 2016). It also agrees with the observation of reduced hippocampal volume during pregnancy in rats, when estradiol, alongside other sex hormones, is elevated (Galea et al., 2000;Rolls et al., 2008). However, they are in contrast to other studies which have shown that higher estradiol concentration is associated with larger hippocampal volumes and propose a neuroprotective effect of estradiol (Barth et al., 2016;Bayer et al., 2013;Galea et al., 2013;Kesler et al., 2004). ...
Article
Full-text available
Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS)summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals. Using this data, we generated polygenic risk scores (PRS)for estradiol, progesterone, prolactin and testosterone in the European RADIANT cohort consisting of 176 postpartum depression (PPD)cases (100% female, mean age: 41.6 years old), 2772 major depressive disorder (MDD)cases (68.6% female, mean age: 46.9 years old)and 1588 control participants (62.5% female, mean age: 42.4 years old), for which there was also a neuroimaging subset of 111 individuals (60.4% female, mean age: 50.0 years old). Only the best-fit PRS for estradiol showed a significant negative association with hippocampal volume, as well as many of its individual subfields; including the molecular layer and granule cell layer of the dentate gyrus, subiculum, CA1, CA2/3 and CA4 regions. Interestingly, several of these subfields are implicated in adult hippocampal neurogenesis. When we tested the same estradiol PRS for association with case-control status for PPD or MDD there was no significant relationship observed. Here, we provide evidence that genetic risk for higher plasma estradiol is negatively associated with hippocampal volume, but this does not translate into an increased risk of MDD or PPD. This work suggests that the relationship between reproductive hormones, the hippocampus, and depression is complex, and that there may not be a clear-cut pathway for etiology or risk moderation.
... Durante la etapa de embarazo existe poca literatura que aborde estas alteraciones, sin embargo, existen hallazgos respecto a la función cognitiva. Galea et al. (2000), Hammer, Mateo y Bridges (1992) observaron en modelos experimentales cambios neurales en la madre durante la gestación, que a su vez podrían ser reflejo de las modificaciones en la memoria y de las hormonas. ...
... En un estudio en donde se utilizó resonancia magnética Oatridgel et al. (1998) encontraron una recuperación en el tamaño del cerebro 6 -8 semanas después del parto, en comparación con el tamaño del cerebro durante el tercer trimestre del embarazo en humanos. Por su parte Galea et al. (2000) compararon en ratas gestantes y no gestantes el rendimiento de la memoria a través del laberinto de ...
... In addition to the similarities between the molecules regulating memory and maternal behavior, there is evidence that spatial memory is affected peripartum (Perani and Slattery, 2014). Pregnant rats perform better than virgin females in spatial memory tasks during the first two trimesters of pregnancy (Galea et al., 2000). However, maternal memory is impaired in the last trimester of pregnancy and after the delivery (Galea et al., 2000;Darnaudery et al., 2007), somewhat similar to studies in humans, showing that some memories are diminished during pregnancy and after parturition (Glynn, 2010). ...
... Pregnant rats perform better than virgin females in spatial memory tasks during the first two trimesters of pregnancy (Galea et al., 2000). However, maternal memory is impaired in the last trimester of pregnancy and after the delivery (Galea et al., 2000;Darnaudery et al., 2007), somewhat similar to studies in humans, showing that some memories are diminished during pregnancy and after parturition (Glynn, 2010). Therefore, it is possible that an increase in memory processes devoted to maternal care takes a toll on other brain functions, including spatial memory, as pregnancy, giving birth and caring for the progeny require and consume significant energetic resources. ...
Article
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Maternal behavior is shaped and challenged by the changing developmental needs of offspring and a broad range of environmental factors, with evidence indicating that the maternal brain exhibits a high degree of plasticity. This plasticity is displayed within cellular and molecular systems, including both intra- and intercellular signaling processes as well as transcriptional profiles. This experience-associated plasticity may have significant overlap with the mechanisms controlling memory processes, in particular those that are activity-dependent. While a significant body of work has identified various molecules and intracellular processes regulating maternal care, the role of activity- and experience-dependent processes remains unclear. We discuss recent progress in studying activity-dependent changes occurring at the synapse, in the nucleus, and during the transport between these two structures in relation to maternal behavior. Several pre- and postsynaptic molecules as well as transcription factors have been found to be critical in these processes. This role reflects the principal importance of the molecular and cellular mechanisms of memory formation to maternal and other behavioral adaptations.
... In general, early-and mid-pregnancy (lower levels of estradiol) are associated with enhanced spatial performance, but the opposite is true during late pregnancy (higher levels of estradiol; Galea et al., 2000;Macbeth et al., 2008). Additionally, the early postpartum period is characterized by impaired hippocampus-dependent learning, while the late postpartum period and after weaning are characterized by enhanced hippocampus-dependent learning compared to non-parous rats (Darnaudéry et al., 2007;Kinsley et al., 1999;Gatewood et al., 2005;Kinsley et al., 2012). ...
... The brain changes drastically across pregnancy and the postpartum period. Hippocampal volume is significantly reduced in pregnant rats (Galea et al., 2000) and overall brain volume is reduced in humans but returns to pre-pregnancy level after parturition (Oatridge et al., 2002). In mice, BrdU-labeled cell survival is decreased during the second week of gestation but returns to nulliparous levels 21 days after parturition (Rolls et al., 2008). ...
Article
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Steroid and peptide hormones modulate neurogenesis in the dentate gyrus differentially in male and female adult rodents. Neurogenesis is comprised of at least two components: cell proliferation (the production of new cells) and cell survival (which ultimately results in changes to the number of new neurons that survive to maturity). This chapter focuses on the effects of estrogens, androgens, adrenal steroids, and peptide hormones on hippocampal neurogenesis in the adult male and female rodent. Evidence is reviewed for the co-localization of hormone receptors with markers for neurogenesis to indicate possible mechanisms by which hormones exert their effects to modulate neurogenesis. Estradiol modulates hippocampal neurogenesis and cell death in adult female, but not male, rodents, while testosterone upregulates hippocampal neurogenesis in adult male rodents. Few studies have compared males and females, but existing research suggests a sex difference in the response to stress-regulated hippocampal neurogenesis in the adult. More work is needed to elucidate the effects of hormones on neurogenesis in the dentate gyrus of both male and female rodents across the life span. This is crucial if we are to use our knowledge of how adult neurogenesis is regulated to develop strategies to replace neuron loss in neurodegenerative diseases, which often exhibit sex differences in disease incidence, symptomology, and/or progression.
... Therefore, hippocampal plasticity across the peripartum period is likely to underlie changes in cognition, spatial abilities, memory and perhaps maternal behaviour. Taking the literature together, hippocampal-dependent spatial memory is impaired during late gestation and the early postpartum period (Darnaudery et al., 2007;Galea et al., 2000), but enhanced during the late postpartum period (Galea et al., 2000;Kinsley et al., 1999). Assessing hippocampal neurogenesis, spatial reference and working memory in nulli-, primi-and multi-parous rats, Pawluski et al. convincingly demonstrated that parity is an essential factor affecting both parameters. ...
... Therefore, hippocampal plasticity across the peripartum period is likely to underlie changes in cognition, spatial abilities, memory and perhaps maternal behaviour. Taking the literature together, hippocampal-dependent spatial memory is impaired during late gestation and the early postpartum period (Darnaudery et al., 2007;Galea et al., 2000), but enhanced during the late postpartum period (Galea et al., 2000;Kinsley et al., 1999). Assessing hippocampal neurogenesis, spatial reference and working memory in nulli-, primi-and multi-parous rats, Pawluski et al. convincingly demonstrated that parity is an essential factor affecting both parameters. ...
... Female O. lunatus of this study included lactating individuals, a condition characterized by important changes in circulating hormones, hippocampal anatomy and cognition [Roes and Galea, 2016]. Previous studies revealed how low estradiol and high progesterone levels increase spatial ability in pregnant rats [Galea et al., 2000], and Hamilton et al. [1977] demonstrated that lactating rats had increased cortical thickness compared with nonbreeding rats. Thus, potential hormonal differences associated with these different breeding stages may have translated into various volumes in neuroanatomical structures linked to the construction of cognitive maps for navigation [McEwen, 2002]. ...
Article
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Navigational and social challenges due to habitat conditions and sociality are known to influence dentate gyrus (DG) morphology, yet the relative importance of these factors remains unclear. Thus, we studied three natural populations of O. lunatus (Los Molles) and Octodon degus (El Salitre and Rinconada), two caviomorph species that differ in the extent of sociality and with contrasting vegetation cover of habitat used. The brains and DG of male and female breeding degus with simultaneous information on their physical and social environments were examined. The extent of sociality was quantified from total group size and range area overlap. O. degus at El Salitre was more social than at Rinconada and than O. lunatus from Los Molles. The use of transects to quantify cover of vegetation (and other physical objects in the habitat) and measures of the spatial behavior of animals indicated animal navigation based on unique cues or global landmarks is more cognitively challenging to O. lunatus. During lactation, female O. lunatus had larger brains than males. Relative DG volume was similar across sexes and populations. The right hemisphere of male and female O. lunatus had more cells than the left hemisphere, with DG directional asymmetry not found in O. degus. Degu population differences in brain size and DG cell number seemed more responsive to differences in habitat than to differences in sociality. Yet, large-sized O. degus (but not O. lunatus) that ranged over larger areas and were members of larger social groups had more DG cells per hemisphere. Thus, within-population variation in DG cell number by hemisphere was consistent with a joint influence of habitat and sociality in O. degus at El Salitre.
... At parturition, estradiol levels drop abruptly and remain low during the postpartum period (Bloch et al., 2003). Not surprisingly, the maternal brain undergoes numerous structural and functional changes, including gross neuroplastic changes such as reduced hippocampal volume in rats (Galea et al., 2000), and a transient reduction in overall brain volume in women (Oatridge et al., 2002). In addition, changes in dendritic morphology and spine densities in the CA1 and CA3 regions are detected with primiparous (pregnant once) rats exhibiting reductions compared to nulliparous and multiparous (pregnant more than once) rats (Pawluski and Galea, 2006). ...
... Thus, our study suggests that maternal neuroendocrine systems are buffered from stress during the first two thirds of gestation. Indeed, across mammalian species, including humans, extensive morphological and functional central changes occur during pregnancy (Zingg et al., 1995;Galea et al., 2000;Grattan et al., 2001;Oatridge et al., 2002;Kokay et al., 2006;Pawluski et al., 2009;Hillerer et al., 2014;Kim, 2016), and during late gestation, these changes include an attenuated HPA response to a variety of stressors (Douglas et al., 1998). Because our study focused on early to midgestation with dams displaying a robust change in production of glucocorticoids, HPA axis attenuation cannot explain out results, and instead our data point to a novel system responsible for buffering the effects of stress on maternal physiology. ...
Article
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Psychological stress, both leading up to and during pregnancy, is associated with increased risk for negative pregnancy outcomes. Although the neuroendocrine circuits that link the stress response to reduced sexual motivation and mating are well-described, the specific pathways by which stress negatively impacts gestational outcomes remain unclear. Using a mouse model of chronic psychological stress during pregnancy, we investigated 1) how chronic exposure to stress during gestation impacts maternal reproductive neuroendocrine circuitry, and 2) whether stress alters developmental outcomes for the fetus or placenta by mid-pregnancy. Focusing on the stress-responsive neuropeptide RFRP-3, we identified novel contacts between RFRP-3-immunoreactive (RFRP-3-ir) cells and tuberoinfundibular dopaminergic neurons in the arcuate nucleus, thus providing a potential pathway linking the neuroendocrine stress response directly to pituitary prolactin production and release. However, neither of these cell populations nor circulating levels of pituitary hormones were affected by chronic stress. Conversely, circulating levels of steroid hormones relevant to gestational outcomes (progesterone and corticosterone) were altered in chronically-stressed dams across gestation, and those dams were qualitatively more likely to experience delays in fetal development. Together, these findings suggest that, up until at least mid-pregnancy, mothers appear to be relatively resilient to the effects of elevated glucocorticoids on reproductive neuroendocrine system function. We conclude that understanding how chronic psychological stress impacts reproductive outcomes will require understanding individual susceptibility and identifying reliable neuroendocrine changes resulting from gestational stress.
... However, neurogenesis may only play a minor role in cognitive changes during other peripartum times. For example, variations in spatial abilities are evident across pregnancy in rats when neither cell proliferation nor survival are altered (Galea et al., 2000;Bodensteiner et al., 2006;Paris and Frye, 2008). Likewise, primiparous female rats during the late postpartum period outperform nulliparous females on spatial tasks despite comparable levels of cell proliferation and reduced cell survival (Kinsley et al., 1999;Darnaudery et al., 2007;Leuner et al., 2007;Pawluski and Galea, 2007;Hillerer et al., 2014). ...
... Progesterone alone or in combination with estrogen improves performance in water mazes. 23,[28][29][30]32,[34][35][36][37][38] Any beneficial effect of progesterone may come after its conversion to a metabolite 31,66 and through that metabolite's agonistic action at GABA A receptors, 67 which are inhibitory in adult mammals. It should be noted, however, that not all studies have found progesterone to benefit escape in a Morris water maze. ...
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In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action.
... In paradigms that test spatial memory, parous rats that had weaned their pups days, weeks, or even months before acquisition make fewer reference and/or working memory errors compared to nulliparous females (Gatewood et al., 2005;Kinsley et al., 1999;Lemaire et al., 2006;Love et al., 2005;Pawluski et al., 2006a,b; but for opposite results see Bodensteiner et al., 2006;Darnaudéry et al., 2007). A combination of mothering experience and the hormones of reproduction appear to contribute to the enhanced memory because 1) it is unclear if learning or memory are enhanced in pregnant rats (Bodensteiner et al., 2006;Galea et al., 2000), 2) such effect are not found in females whose pups were removed soon after parturition (Pawluski et al., 2006a), and 3) nulliparous sensitized females also show enhanced spatial memory if they are tested within a few days after their final interaction with pups (Kinsley et al., 1999;Lambert et al., 2005), but this enhancement does not persist as long as it does in female rats with both reproductive and maternal experience (Pawluski et al., 2006a). ...
Article
Maternal interactions with young occupy most of the reproductive period for female mammals and are absolutely essential for offspring survival and development. The hormonal, sensory, reward-related, emotional, cognitive and neurobiological regulators of maternal caregiving behaviors have been well studied in numerous subprimate mammalian species, and some of the importance of this body of work is thought to be its relevance for understanding similar controls in humans. We here review many of the important biopsychological influences on maternal behaviors in the two best studied non-human animals, laboratory rats and sheep, and directly examine how the conceptual framework established by some of the major discoveries in these animal "models" do or do not hold for our understanding of human mothering. We also explore some of the limits for extrapolating from non-human animals to humans. We conclude that there are many similarities between non-human and human mothers in the biological and psychological factors influencing their early maternal behavior and that many of the differences are due to species-characteristic features related to the role of hormones, the relative importance of each sensory system, flexibility in what behaviors are exhibited, the presence or absence of language, and the complexity of cortical function influencing the behavior.
... In paradigms that test spatial memory, parous rats that had weaned their pups days, weeks, or even months before acquisition make fewer reference and/or working memory errors compared to nulliparous females (Gatewood et al., 2005;Kinsley et al., 1999;Lemaire et al., 2006;Love et al., 2005;Pawluski et al., 2006a,b; but for opposite results see Bodensteiner et al., 2006;Darnaudéry et al., 2007). A combination of mothering experience and the hormones of reproduction appear to contribute to the enhanced memory because 1) it is unclear if learning or memory are enhanced in pregnant rats (Bodensteiner et al., 2006;Galea et al., 2000), 2) such effect are not found in females whose pups were removed soon after parturition (Pawluski et al., 2006a), and 3) nulliparous sensitized females also show enhanced spatial memory if they are tested within a few days after their final interaction with pups (Kinsley et al., 1999;Lambert et al., 2005), but this enhancement does not persist as long as it does in female rats with both reproductive and maternal experience (Pawluski et al., 2006a). ...
Article
Maternal interactions with young occupy most of the reproductive period for female mammals and are absolutely essential for offspring survival and development. The hormonal, sensory, reward-related, emotional, cognitive and neurobiological regulators of maternal caregiving behaviors have been well studied in numerous subprimate mammalian species, and some of the importance of this body of work is thought to be its relevance for understanding similar controls in humans. We here review many of the important biopsychological influences on maternal behaviors in the two best studied non-human animals, laboratory rats and sheep, and directly examine how the conceptual framework established by some of the major discoveries in these animal "models" do or do not hold for our understanding of human mothering. We also explore some of the limits for extrapolating from non-human animals to humans. We conclude that there are many similarities between non-human and human mothers in the biological and psychological factors influencing their early maternal behavior and that many of the differences are due to species-characteristic features related to the role of hormones, the relative importance of each sensory system, flexibility in what behaviors are exhibited, the presence or absence of language, and the complexity of cortical function influencing the behavior. Copyright © 2015. Published by Elsevier Inc.
... Last thirty years, it has been shown that in female rats, pregnancy causes behavioral changes in response to different environmental stimuli [1]. Galea et al. [2] found an increase in memorable performances in the Morris maze test. A reduction in anxiety was also reported in elevated plus maze [3]. ...
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Hacène Frih, Asma Latreche, Bachir Ali Rachedi, Rédha Djenidi, Leila Sahraoui and Abdelkrim Tahraoui Background: The endocrinal and physiological consequences, following the sub chronic administration of toluene (Tol), were examined in pregnant Wistar rats. Methods: A quarter of lethal dose concentration (LD50) of toluene was injected daily in IP to pregnant rats between the 4th and the 14th day of pregnancy. Virgin female rats were also used as a basis of comparison and obey to the same experimental protocol. Blood samples and recordings of sequences of behavior in elevated plus maze was made in 7th, 14th and 21st day of pregnancy. The measurement of the serum levels of progesterone were carried out at the 7th day of gestation (3rd day of treatment), the 14th day (last day of treatment) and one week after delivery (14th day after discontinuation of therapy). After delivery, which occurs at the 21st day, we tested the effectiveness of a GABAergique agonist, the clonazepam, during the forced swimming test. Results: Our results showed that the application of toluene neurotoxic stress during 10 days caused endocrine (plasma progesterone) and behavior (anxiety) disruption that appear to be irreversible in virgin female rats treated with toluene. For cons, the same treatment associated with pregnancy revealed a healing effect 14 days after stopping treatment. Inefficiency of both clonazepam and toluene treatment in virgin female rats was observed. This treatment was effective in pregnant rats treated only with toluene. Conclusion: Pregnancy appears to play a moderating effect on harmfulness and neurotoxicity of toluene, by protecting GABAergic route. Progesterone, as a neuroactif steroid, plays an important role in this protection
... Although it is still unclear why the brain size and volume decreased during pregnancy among human mothers, animal work suggests that hormonal changes for reproduction are associated with neural plasticity in the maternal brain during pregnancy (Leuner, Glasper, & Gould, 2010). Increased levels of estradiol and corticosterone have been associated with decreased volume and suppressed cell proliferation in the hippocampus during pregnancy (Galea et al., 2000;Pawluski, Brummelte, Barha, Crozier, & Galea, 2009). ...
New mothers undergo dynamic neural changes that support positive adaptation to parenting and the development of mother-infant relationships. In this article, I review important psychological adaptations that mothers experience during pregnancy and the early postpartum period. I then review evidence of structural and functional plasticity in human mothers' brains, and explore how such plasticity supports mothers' psychological adaptation to parenting and sensitive maternal behaviors. Last, I discuss pregnancy and the early postpartum period as a window of vulnerabilities and opportunities when the human maternal brain is influenced by stress and psychopathology, but also receptive to interventions.
... For example, pregnant rats have been reported to outperform nonpregnant female rats on tests of memory and cognition (13). Other animal studies have shown morphological brain changes during pregnancy in the absence of functional memory impairment (14). ...
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Attention deficit hyperactivity disorder (ADHD) has been increasingly recognized and treated in children and adults in recent years. As a result, a growing number of women enter their reproductive years treated with medication for ADHD or are diagnosed and start medication during their reproductive years. A common question in perinatal psychiatry regards the risk-benefit profile of pharmacotherapy for ADHD, particularly with stimulants. At this time, there are no guidelines to inform the treatment of ADHD across pregnancy and the postpartum period. Concerns about in utero exposure to stimulants are based primarily on the impact these medications might have on fetal growth. While stimulants do not appear to be associated with major congenital malformations, more human data regarding potential behavioral teratogenicity are needed in order to understand both the short- and long-term risks. Severity of illness, presence of comorbid disorders, and degree of impairment have an impact on treatment decisions. Crucial considerations include driving safety and ability to function in occupational roles. While most women can successfully avoid the use of stimulant medication during pregnancy, there are cases in which the benefits of stimulant treatment outweigh known and putative risks of in utero medication exposure.
... Reductions and subsequent increases in neurogenesis can also be hypothesized to contribute to some of the observed hippocampal volume change in our study. In accordance with our findings, animal studies investigating the volume of the hippocampus observed a trend for hippocampal volume reduction during late pregnancy 44 and in lactating primiparous rats in the postpartum period in comparison to nulliparous females 45 . Aged parous rats-especially multiparous females-were found to have increased hippocampal long-term potentiation, enhanced memory capacities and less signs of brain aging in comparison to aged nulliparous females [17][18][19][20][21]38 . ...
Article
Pregnancy involves radical hormone surges and biological adaptations. However, the effects of pregnancy on the human brain are virtually unknown. Here we show, using a prospective ('pre'-'post' pregnancy) study involving first-time mothers and fathers and nulliparous control groups, that pregnancy renders substantial changes in brain structure, primarily reductions in gray matter (GM) volume in regions subserving social cognition. The changes were selective for the mothers and highly consistent, correctly classifying all women as having undergone pregnancy or not in-between sessions. Interestingly, the volume reductions showed a substantial overlap with brain regions responding to the women's babies postpartum. Furthermore, the GM volume changes of pregnancy predicted measures of postpartum maternal attachment, suggestive of an adaptive process serving the transition into motherhood. Another follow-up session showed that the GM reductions endured for at least 2 years post-pregnancy. Our data provide the first evidence that pregnancy confers long-lasting changes in a woman's brain.
... Pregnancy is associated with memory impairment (Henry & Rendell, 2007). This impairment is most common for memory tasks that require higher-order executive control processes (Anderson & Rutherford, 2012) and is more prevalent during the later stages of pregnancy (Galea et al., 2000). Encouragingly, exercise has been shown to enhance memory function among the general population (Frith, Sng, & Loprinzi, 2017;Loprinzi, Edwards, & Frith, 2017;Loprinzi, Ponce, & Frith, 2018) and improve cognition-related cardiovascular disease risk factors among pregnant women (Loprinzi, Fitzgerald, Woekel, & Cardinal, 2013). ...
... Data from other research (Boldrini et al., 2018;Spalding et al., 2013) leave the relationships between adult hippocampal neurogenesis, hippocampal volume, and hippocampal functions open for study and consideration (Cuttler, Graf, Pawluski, & Galea, 2011;Henry & Sherwin, 2012) in humans. However, hippocampal volume does not differ between pregnant and non-pregnant rats (Galea et al., 2000), so more work is needed to determine the mechanisms of cognitive impairment associated with pregnancy and the specific differences between species in the hippocampal neurogenesis in reproductive situations, and to determine the role for prolactin in these changes. ...
Chapter
Prolactin (PRL) is a pituitary hormone that has been typically related to lactogenesis in mammals. However, it has been described over 300 roles in the organism of vertebrae and its relationship with the central nervous system (CNS) is yet to be clarified. Mainly secreted by the pituitary gland, the source of prolactin in the CNS remains unclear, where some experiments suggest active transport via an unknown carrier or, on the contrary, PRL being synthesized on the brain. So far, it seems to be involved with neurogenesis, neuroprotection, maternal behavior and cognitive processes in the hippocampus and dentate gyrus, among other regions.
... ., 1999). Esto puede afectar posiblemente el rendimiento de la memoria, la cual es capacidad de recuperar informaci?n mediante procesos neurobiol?gicos de almacenamiento (Etchepareborda & AbadMas, 2005). Durante la etapa de embarazo existe poca literatura que aborde estas alteraciones, sin embargo, existen hallazgos respecto a la funci?n cognitiva.Galea et al. (2000), Hammer, Mateo y Bridges (1992) observaron en modelos experimentales cambios neurales en la madre durante la gestaci?n, que a su vez podr?an ser reflejo de las modificaciones en la memoria y de las hormonas. Adem?s, se ha encontrado en la madre que durante la ?ltima fase de la gestaci?n existe una disminuci?n en el tama?o de la masa cer ...
... Areas where BrdU + cells (subgranular zone and granule cell layer) and Iba1 + microglia (granule cell layer and hilus) were counted were measured under a 10x objective using MicroBrightfield StereoInvestigator software (Williston, VT, USA) to calculate cell densities for comparison with OB measures. In addition, dentate gyrus volumes were estimated using Cavalieri's principle (Uylings et al., 1986;Galea et al., 2000;Seifert et al., 2010) ...
Article
We tested whether indomethacin or rosiglitazone treatment could rejuvenate spatial ability and hippocampal neurogenesis in aging rats. Young (4 mo; n = 30), middle-aged (12 mo; n = 31), and aged (18 mo; n = 31) male Fischer 344 rats were trained and then tested in a rapid acquisition water maze task and then fed vehicle (500 µl strawberry milk), indomethacin (2.0 mg/ml), or rosiglitazone (8.0 mg/ml) twice daily for the remainder of the experiment. A week after drug treatment commenced, the rats were given 3 daily BrdU (50 mg/kg) injections to test whether age-related declines in neurogenesis were reversed. One week after the final BrdU injection (∼2.5 weeks after the 1st water maze session), the rats were trained to a find novel hidden water maze platform location, tested on 15 min and 24 h probe trials and then killed 24 h later. During the first water maze session, young rats outperformed aged rats but all rats learned information about the hidden platform location. Middle-aged and aged rats exhibited better memory probe trial performances than young rats in the 2nd water maze session and indomethacin improved memory probe trial performances on the 2nd vs. 1st water maze session in middle-aged rats. Middle-aged rats with more new neurons had fewer phagocytic microglia and exhibited better hidden platform training trial performances on the 2nd water maze session. Regardless of age, indomethacin increased new hippocampal neuron numbers and both rosiglitazone and indomethacin increased subependymal neuroblasts/neuron densities. Taken together, our results suggest the feasibility of studying the effects of longer-term immunomodulation on age-related declines in cognition and neurogenesis.
... A meta-analysis by Davies et al. (2018) reports, for instance, that the overall cognitive function (memory, executive function and attention) is poorer in pregnant women compared with their nonpregnant counterparts, especially during the third trimester. On the level of brain morphology, our results along with those of animal studies suggest that pregnancy triggers (at least transitorily) a reduction of hippocampal volume (Galea et al. 2000;Barrière et al. 2021). However, it is unclear if the GMV reduction in the hippocampus or any other brain structure has any short-or long-term effect on the cognitive function of young mothers. ...
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There is growing evidence that pregnancy may have a significant impact on the maternal brain, causing changes in its structure. To investigate the patterns of these changes, we compared nulliparous women (n = 40) with a group of primiparous women (n = 40) and multiparous mothers (n = 37) within 1-4 days postpartum, using voxel-based and surface-based morphometry (SBM). Compared with the nulliparous women, the young mothers showed decreases in gray matter volume in the bilateral hippocampus/amygdala, the orbitofrontal/subgenual prefrontal area, the right superior temporal gyrus and insula, and the cerebellum. These pregnancy-related changes in brain structure did not predict the quality of mother-infant attachment at either 3 or 12 weeks postpartum nor were they more pronounced among the multiparous women. SBM analyses showed significant cortical thinning especially in the frontal and parietal cortices, with the parietal cortical thinning likely potentiated by multiple pregnancies. We conclude that, compared with the brain of nulliparous women, the maternal brain shows widespread morphological changes shortly after childbirth. Also, the experience of pregnancy alone may not be the underlying cause of the adaptations for mothering. As regards the exact biological function of the changes in brain morphology, longitudinal research will be needed to draw any definitive conclusions.
... In a study showing that late pregnant female rats (day 21) have poorer working memory compared to their non-pregnant counterparts, Galea et al. reported a strong trend toward reduced hippocampal volume in late-pregnant rats (Galea et al., 2000). This work predated the research in women showing that hippocampal volume is reduced across pregnancy (Hoekzema et al., 2017) and points to an effect of pregnancy on the hippocampus that is conserved across mammals. ...
Article
PAWLUSKI, J.L., Hoekzema, E., Leuner, B,. and Lonstein, J.S. Less can be more: Fine tuning the maternal brain. NEUROSCI BIOBEHAV REV (129) XXX-XXX, 2022. Plasticity in the female brain across the lifespan has recently become a growing field of scientific inquiry. This has led to the understanding that the transition to motherhood is marked by some of the most significant changes in brain plasticity in the adult female brain. Perhaps unexpectedly, plasticity occurring in the maternal brain often involves a decrease in brain volume, neurogenesis and glial cell density that presumably optimizes caregiving and other postpartum behaviors. This review summarizes what we know of the ‘fine-tuning’ of the female brain that accompanies motherhood and highlights the implications of these changes for maternal neurobehavioral health. The first part of the review summarizes structural and functional brain changes in humans during pregnancy and postpartum period with the remainder of the review focusing on neural and glial plasticity during the peripartum period in animal models. The aim of this review is to provide a clear understanding of when ‘less is more’ in maternal brain plasticity and where future research can focus to improve our understanding of the unique brain plasticity occurring during matrescence.
... Con la experiencia reproductiva, la gran concentración de receptores de hormonas esteroideas y peptídicas aumentan la sensibilidad del hipocampo a las fluctuaciones hormonales, pudiendo ser modificado en su estructura y plasticidad 3,47,51,52 . Por otra parte, en cuanto a la morfología cerebral, se ha demostrado en roedores que el tamaño total del cerebro disminuye durante el embarazo y vuelve al tamaño preconcepcional durante el período postparto 43,53 . ...
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Las modificaciones neurobiológicas que experimenta la mujer durante el puerperio, junto con los consecuentes cambios psicosociales, determinan variaciones en el funcionamiento cognitivo. Con el objetivo de describir las variaciones cognitivas que ocurren durante el postparto y sus factores determinantes, se desarrolló una revisión narrativa a partir de la búsqueda bibliográfica en PubMed y Google Scholar. Se evidenció un constante crecimiento del número de publicaciones a lo largo de los años (PubMed= 186; Google Scholar= 26730). El análisis de los artículos permitió: a) Caracterizar las funciones cognitivas durante el puerperio; b) Analizar los efectos neuropsicológicos producidos por los cambios endocrinológicos y anatomofisiológicos; c) Analizar el efecto de la calidad del sueño sobre la cognición; d) Analizar las funciones cognitivas en función de las experiencias obstétricas. En conclusión, la mujer puérpera se caracteriza por presentar variaciones en sus funciones cognitivas, las cuales están determinadas por cambios estructurales, funcionales, psicológicos y sociales. Es necesario fomentar investigaciones neuropsicológicas en esta población, ya que la atención del posparto todavía se centra en el cuidado del recién nacido, sin abordar a la mujer puérpera de manera integral.
... A study in wild meadow voles (Microtus pennsylvanicus) found decreased levels of hippocampal cell proliferation in pregnant females compared to non-pregnant controls and a significant negative correlation between circulating levels of corticosterone and hippocampal cell proliferation (Galea & McEwen, 1999). A study in rats demonstrated impaired hippocampal-dependent spatial working memory during late gestation and decreased hippocampal volume during pregnancy (Galea et al., 2000). ...
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Life‐history theory predicts that access to limited resources leads to trade‐offs between competing body functions. Women, who face higher costs of reproduction when compared to men, should be especially vulnerable to these trade‐offs. We propose the ‘cognitive costs of reproduction hypothesis’, which states that energy trade‐offs imposed by reproduction may lead to a decline in maternal cognitive function during gestation. In particular, we hypothesize that the decline in cognitive function frequently observed during pregnancy is associated with the allocation of resources between the competing energetic requirements of the mother's brain and the developing foetus. Several distinctive anatomical and physiological features including a high metabolic rate of the brain, large infant size, specific anatomical features of the placenta and trophoblast, and the lack of maternal control over glucose flow through the placenta make the occurrence of these trade‐offs likely. Herein, we review several lines of evidence for trade‐offs between gestation and cognition that are related to: (i) energy metabolism during reproduction; (ii) energy metabolism of the human brain; (iii) links between energy metabolism and cognitive function; and (iv) links between gestation and cognitive function. We also review evidence for the important roles of cortisol, corticotropin‐releasing hormone and sex hormones in mediating the effects of gestation on cognition, and we discuss possible neurophysiological mechanisms underlying the observed effects. The evidence supports the view that energy trade‐offs between foetal growth and maternal endocrine and brain function lead to changes in maternal cognition, and that this phenomenon is mediated by neuroendocrine mechanisms involving the hypothalamic–pituitary–adrenal axis, brainstem nucleus locus coeruleus and hippocampus.
... A portion of the hippocampus (left hippocampal cluster) returned to prepregnancy baseline volume by 2 years postpartum (Hoekzema et al., 2017). Similarly, the hippocampus has been characterized by a reduction in both cell proliferation and volume during pregnancy and the peripartum period in rodents (Galea et al., 2000;Rolls et al., 2008). Research in rodents has indicated alterations in the neurogenesis of hippocampal neurons in both mothers and fathers during the postpartum period (Glasper et al., 2011). ...
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Pregnancy and the transition to parenthood is an important period marked by dramatic neurobiological and psychosocial changes that may have implications for the health of women and offspring. Although human and non-human animal research suggests the brain undergoes alterations during the peripartum period, these changes are poorly understood. Here, we review existing research, particularly human neuroimaging and psychophysiological research, to examine changes in brain structure and function during the peripartum period and discuss potential implications for the health of women and offspring. First, we discuss the potential causes of these changes across pregnancy, including physiological and psychosocial factors. Next, we discuss the evidence for structural and functional changes in the brain during pregnancy and into the postpartum period, noting the need for research conducted prospectively across human pregnancy. Finally, we propose potential models of individual differences in peripartum neurobiological changes (i.e., hypo-response, typical response, hyper-response) and emphasize the need to consider trajectories of change in addition to pre-existing factors that may predict maternal adjustment to parenthood. We suggest that the consideration of individual differences in neurobiological trajectories across pregnancy may contribute to a better understanding of risk for negative health and behavior outcomes for women and offspring.
... Chez les rats femelles, la gestation engendre des changements comportementaux en réponse aux différents stimuli de l'environnement [6]. Galea et al. [7] ont constaté une augmentation des performances mémoratives au test du labyrinthe de Morris. Une réduction de l'anxiété a été également signalée au labyrinthe en croix surélevé [8]. ...
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Révisé le 17/12/2011 Accepté le 07/05/2012 ‫ملخص‬ ‫جزعخ‬ ‫رثع‬ ٍ‫حق‬ ‫رى‬ ‫نقذ‬ ‫يًُزخ‬ ٍَ‫انزىنى‬ ‫نًبدح‬ ‫نهفأراد‬ ‫رى‬ ‫وَظزبر‬ ٌ‫فئزا‬ ‫فُشَىنىجُب‬ ‫و‬ ٍ‫انعصج‬ ٌ‫انغذ‬ ‫انجهبس‬ ً‫عه‬ ٍَ‫انزىنى‬ ‫يبدح‬ ‫رأصُز‬ ‫عىاقت‬ ‫فحص‬ ‫انُىو‬ ٍ‫ي‬ ‫انًًزذح‬ ‫انحًم‬ ‫فززح‬ ‫خالل‬ ‫انحىايم‬ 4 ‫َىو‬ ً‫إن‬ 14 ‫األَبو‬ ٍ‫ف‬ ‫انحًم‬ ٍ‫ي‬ 7 ‫انحًم‬ ٍ‫ي‬ (ٍَ‫ثبنزىنى‬ ‫انًعبيهخ‬ ٍ‫ي‬ ‫َىو‬ ‫صبنش‬) , 14 (ٍ‫ي‬ ‫انعبشز‬ ‫انُىو‬ ‫انًعبيهخ‬) ‫و‬ 21 (10 ‫انًعبيهخ‬ ‫إَقبف‬ ‫ثعذ‬ ‫أَبو‬). ٌ‫انجزوجظززو‬ ٌ‫هزيى‬ ‫يظزىَبد‬ ‫قُبص‬ ‫نغزض‬ ‫ديىَخ‬ ‫فحىصبد‬ ‫أجزَذ‬ ‫و‬ LH (‫َفزس‬ ٌ‫هزيى‬ ‫انُخبيُخ‬ ‫انغذح‬ ‫ثىاططخ‬ .) ‫انىالدح‬ ‫ثعذ‬ , ‫كهىَبسَجبو‬ ‫نالكزئبة‬ ‫يعبد‬ ‫يخذر‬ ‫دواء‬ ‫اخزجبر‬ ‫رى‬ ‫انًهشيخ‬ ‫انظجبحخ‬ ‫اخزجبر‬ ‫حصخ‬ ‫خالل‬. ٌ‫أ‬ ً‫عه‬ ‫انُزبئج‬ ‫أثذد‬ ‫نًذح‬ ٍ‫يشي‬ ‫إجهبد‬ ‫رطجُق‬ 10 ‫انهزيىَبد‬ ‫يظزىي‬ ‫و‬ ‫األععبء‬ ٌ‫وس‬ ٍ‫ف‬ ‫رذهىر‬ ‫َظجت‬ ٍَ‫انزىنى‬ ‫يبدح‬ ‫ثىاططخ‬ ‫أَبو‬ ٌ‫انجزوجظززو‬ ‫و‬ LH ‫انفأراد‬ ‫عُذ‬ ‫حىايم‬ ‫انغُز‬. ‫انقذرح‬ ‫ثُفض‬ ‫فعبل‬ ‫وغُز‬ ٍ‫ظزف‬ ٌ‫َكى‬ ٍَ‫انزىنى‬ ‫فزأصُز‬ ‫انحىايم‬ ‫انفأراد‬ ‫عُذ‬ ‫أيب‬ , ‫َظت‬ ‫اعزذال‬ ً‫إن‬ ٌ‫َؤد‬ ‫يًب‬ ‫يظزىي‬ ‫و‬ ٌ‫انىس‬ ٍ‫ف‬ ٌ ‫انهزيىَبد‬ 10 ‫انًعبيهخ‬ ‫رىقف‬ ‫ثعذ‬ ‫أَبو‬. ‫انغُز‬ ‫انفأراد‬ ‫عُذ‬ ‫انكهىَبسَجبو‬ ‫يبدح‬ ‫فعبنُخ‬ ‫عذو‬ ٍ‫ه‬ ‫انذراطخ‬ ِ‫هذ‬ ‫َزبئج‬ ٍ‫ي‬ ‫اطزخهصذ‬ ‫يهًخ‬ ‫َقطخ‬ ٍَ‫صب‬ ‫يظبر‬ ٍ‫ف‬ ‫خهم‬ ‫إحذاس‬ ً‫عه‬ ‫َذل‬ ‫يًب‬ ٍَ‫ثبنزىنى‬ ‫انًعبيهخ‬ ‫حىايم‬ GABA ٍ‫انعصج‬. ‫ف‬ ‫كجُزا‬ ‫دورا‬ ‫َهعت‬ ‫انحًم‬ ٌ‫أ‬ ‫َجذو‬ ‫انععىَخ‬ ‫حًبَخ‬ ٌ , ‫انغذَخ‬ ‫انظبيخ‬ ٍَ‫انزىنى‬ ‫نًبدح‬ ‫انفأراد‬ ‫رجزع‬ ‫جزاء‬ ‫انًهحقخ‬ ‫انفُشَىنىجُخ‬ ‫األظزار‬ ِ‫ارجب‬ ‫انعصجُخ‬. ‫انحًبَخ‬ ِ‫هذ‬ , ‫هزيىَبد‬ ٍ‫ي‬ ‫انجعط‬ ‫فعبنُزهب‬ ٍ‫ي‬ ‫رشَذ‬ ‫قذ‬ ‫عصجُخ‬ ‫جُظُخ‬ ‫ثهزيىَبد‬ ً‫رذع‬ ‫يؤخزا‬ ‫اكزشبفهب‬ ‫رى‬ ‫انحًم‬ Neuroséroides. ‫ا‬ ‫المفتاحية‬ ‫لكلمات‬ : ‫انظجبح‬ ‫اخزجبر‬ ‫انًهشيخ‬ ‫ح‬-ٌ‫ثزوجظززو‬-ٍَ‫رىنى‬-‫انحًم‬. Résumé Les conséquences neuro-comportementales et physiologiques, suite à l'administration sub chronique du toluène (Tol), ont été examinées chez le rat Wistar femelle gestante. Un quart de la concentration de la DL50 du Tol a été injecté en IP chez les rattes gestante, du 4 ème au 14 ème jour de la gestation. Les prélèvements de sang et la mesure des taux sériques de progestérone et de LH (hormone lutéinisante) ont été réalisées au 7 ème jour de gestation (3ème jour du traitement), au 14 ème jour (dernier jour du traitement) et après la mise bas (10 ème jour après l'arrêt du traitement). Après la mise bas qui coïncide avec le 21 ème jour, nous avons testé l'efficacité d'un agoniste GABAergique, le Clonazepam au cours de la nage forcée (modélisation animal de la dépression). Après décapitation, le cerveau, les surrénales et les ovaires ont été pesés et nous avons calculé les poids relatifs de ces organes. Nos résultats montrent que l'application d'un stress chronique sous toluène a entraîné des perturbations du système endocrinien (taux plasmatiques de LH et de progestérone) et pondérale (poids relatif du cerveau, ovaires et surrénales) qui semblent être irréversibles chez les rattes non gestantes traitées au Tol. Par contre, le même traitement associé à la gestation révèle un effet de rétablissement dix jours après l'arrêt du traitement. L'inefficacité du traitement au Clonazépam enregistrée chez les animaux Tol s'avère efficace chez le lot TolG. La gestation semble jouer un effet modérateur sur la nocivité et la neurotoxicité du toluène, probablement par des neurostéroïdes. Abstract The neuro behavior and physiological consequences, following the sub chronic administration of toluene (Tol), were examined in the pregnant Wistar rats. A quarter lethal dose concentration (LD50) of Tol was injected in IP at the pregnant rats from day 4 to day 14 of gestation. The blood samples and the measurement of the plasma levels of progesterone and luteinizing hormone (LH) were carried out at the 7th day of gestation (3rd day of the treatment), with the 14th day (last day of the treatment) and after delivery (10th day after discontinuation of therapy). After delivery, at the 21st day, the effectiveness of an agonist GABAergique (clonazepam) during the forced swimming test (modelling animal of the depression) was tested. After decapitation, the brain, the adrenals and the ovaries were weighed and the relative weight of these organs was calculated. Our results showed that the application of a sub chronic stress (10 days) by toluene caused endocrine disruption (plasma LH and progesterone) and weight (brain, ovaries and adrenal glands) that appear to be irreversible in non-pregnant animals treated with toluene. However, the same treatment associated with pregnancy reveals a healing effect ten days after stopping treatment. Inefficiency of the treatment with Clonazepam in the Tol animals (virgin treated with toluene), this treatment is effective in TolG group (Pregnant treated with Tol). Gestation appears to play a moderating effect on the harmfulness and the neurotoxicity of toluene, probably by neurosteroids.
... As such, investigations into the effects of estrogens on either behaviour or cellular morphology should take dose response into consideration. Furthermore, longer term exposure to estrogens can similarly have dose dependent responses on learning and memory, with low levels of 17β-estradiol enhancing spatial working memory and high levels of estradiol impairing spatial working and reference memory [150,163,164]. Studies have also shown that, whereas there is dose dependent facilitation in contextual fear conditioning by 17β-and 17α-estradiol, estrone results in dose dependent impairments in contextual fear conditioning [165]. ...
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Sex differences in rats' performance on a stationary hidden-platform task (spatial task) in the Morris water maze and the effects of initial nonstationary hidden platform training (NSP training) were examined. The NSP training was designed to familiarize rats with the general requirements of the water-maze task without providing spatial information. NSP training led to faster acquisition and improved retention of the subsequent spatial task in both males and females. There was a sex difference favoring males on acquisition and retention of the spatial task only in rats that had not received previous NSP training. Moreover, there was an apparent reversed sex difference favoring females on some measures of spatial performance in NSP-trained rats. These results suggest that performance on the water-maze task, including the expression of sex differences, can be altered by previous familiarization with nonspatial aspects of the task.
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Previous studies have shown that estradiol induces new dendritic spines and synapses on hippocampal CA1 pyramidal cells. We have assessed the consequences of estradiol-induced dendritic spines on CA1 pyramidal cell intrinsic and synaptic electrophysiological properties. Hippocampal slices were prepared from ovariectomized rats treated with either estradiol or oil vehicle. CA1 pyramidal cells were recorded and injected with biocytin to visualize spines. The association of dendritic spine density and electrophysiological parameters for each cell was then tested using linear regression analysis. We found a negative relationship between spine density and input resistance; however, no other intrinsic property measured was significantly associated with dendritic spine density. Glutamate receptor autoradiography demonstrated an estradiol-induced increase in binding to NMDA, but not AMPA, receptors. We then used input/output (I/O) curves (EPSP slope vs stimulus intensity) to determine whether the sensitivity of CA1 pyramidal cells to synaptic input is correlated with dendritic spine density. Consistent with the lack of an estradiol effect on AMPA receptor binding, we observed no relationship between the slope of an I/O curve generated under standard recording conditions, in which the AMPA receptor dominates the EPSP, and spine density. However, recording the pharmacologically isolated NMDA receptor-mediated component of the EPSP revealed a significant correlation between I/O slope and spine density. These results indicate that, in parallel with estradiol-induced increases in spine/synapse density and NMDA receptor binding, estradiol treatment increases sensitivity of CA1 pyramidal cells to NMDA receptor-mediated synaptic input; further, sensitivity to NMDA receptor-mediated synaptic input is well correlated with dendritic spine density.
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Recent evidence has demonstrated that there are fluctuations in both the anatomy and physiology of the hippocampus across the estrous cycle of the female rat. In the present study we examined the behavioral implications of these changes by testing females on either a hippocampal or nonhippocampal version of the Morris water maze during the various phases of the estrous cycle. Males were also tested on these tasks. Although there was little variance on the nonhippocampal cue task, females in proestrus performed significantly better than those in estrus. Optimal female performance on the spatial version of the task occurred during the phase of estrus, whereas the least efficient performance occurred during proestrus. These results do not support the traditional view that hippocampal long-term potentiation is positively correlated with spatial learning.
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The present study examined hippocampal volume and dentate gyrus width and their relations to gonadal hormone levels in adult male and female meadow voles, Microtus pennsylvanicus. Females were split into High and Low Estradiol groups based on the median estradiol level. Males were similarly split into High and Low Testosterone groups. Contrary to previous reports in wild meadow voles, there was no evidence of an overall sex difference in hippocampal volume. However, when male-female comparisons were limited to High Testosterone males and Low Estradiol females a significant sex difference in hippocampal volume favouring males did emerge. Hippocampal volume in males was related to testosterone level, with High Testosterone males having significantly larger hippocampi than Low Testosterone males. Similarly, there was a significant influence of plasma estradiol level on hippocampal volume and left dentate gyrus width, with High Estradiol females having larger hippocampi and dentate gyrus width than Low Estradiol females. In addition, consistent with previous findings in the laboratory rat, there were sex differences favouring males in right dentate gyrus width. These findings show that there is a complex relationship between hippocampal volume, dentate gyrus width and gonadal hormone levels in male and female meadow voles.
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Learning based on hippocampal-dependent spatial navigation in female rats was assessed at identified points in the estrous cycle corresponding to low (estrus) and high (proestrus) circulating estrogen. With background training in water-maze procedures, rats learned the location of an escape platform in the maze in a single session of 8 training trials. A strong spatial bias for the escape platform was also evident in a probe trial used to assess retention of learning 30 min after the training session. This entire protocol was completed in less than an hour. The performance of the estrus and proestrus rats was indistinguishable on all behavioral measures, irrespective of the stage of estrous cycle during the task. These results indicate that rapid learning and retention for spatial information over a relatively short interval may be preserved despite morphological alterations in hippocampal dendritic spine density in the normally cycling female rat.
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Repeated restraint stress of rats for 21 days causes atrophy of apical dendrites of hippocampal CA3c pyramidal neurons. This effect is mimicked by daily corticosterone treatment for 21 days and is prevented by the anti-epileptic drug, phenytoin, known to interfere with excitatory amino acid release and action. The present study was designed to investigate the involvement of endogenous corticosterone secretion and excitatory amino acid receptors in the stress-induced hippocampal dendritic atrophy. Treatment of chronically stressed rats with the steroid synthesis blocker cyanoketone prevented stress-induced dendritic atrophy. Cyanoketone-treated animals showed an impaired corticosterone secretion in response to the stressor, while basal levels were maintained. Besides the involvement of endogenous corticosterone secretion, N-methyl-d-aspartate receptors also play a role, since the competitive receptor antagonist, CGP 43487, blocked stress-induced dendritic atrophy. In contrast, NBQX, a competitive inhibitor of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, was ineffective at a dose that blocks ischemic damage.These results indicate that the reversible atrophy induced by 21 days of daily restraint stress requires corticosterone secretion and that excitatory mechanisms involving N-methyl-d-aspartate receptors play a major role in driving the atrophy.
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We addressed the question of how reproductive success (RS) was limited in the shortlived but highly fecund meadow vole, Microtus pennsylvanicus. In so doing, we asked how differential space use patterns could affect longevity and hence RS in each sex. The sample comprised all voles achieving sexual competency over the course of a 40-week breeding season in a live-trapped population in Manomet, MA USA. Matrilineal families were determined using a radionuclide labelling technique; paternity was estimated using a maximum likelihood model. Individual RS was defined as the number of offspring successfully recruited into the trappable population per adult. We found that the variance in RS among female meadow voles was greater than the variance among males. In an attempt to explain this pattern, reproductively successful individuals were compared to reproductively unsuccessful individuals with regard to survivorship, maximum body weight achieved, and spatial mobility. The only difference between fathers and reproductively unsuccessful males was that fathers were heavier. In contrast, mothers differed from unsuccessful females in every measurement. Females lived longer than males, and mothers lived longer than either fathers or reproductively unsuccessful females. The observed differences in longevity may have been largely the result of differences in levels of mobility, assuming more mobile voles were more susceptible to predation. Mothers were significantly more site tenacious than were either males or unsuccessful females. These patterns explain the distribution of RS in our population if predation differentially affects male and female meadow voles. The meadow vole is the only non-polyandrous vertebrate reported to date in which the variance in RS among females exceeds the variance in RS among males.
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Opiate receptor and endogenous opioid content were determined in pregnant, lactating, ovariectomized, and ovariectomized and subsequently estradiol- and progesterone-treated adult female rats. Levels of estradiol and progesterone produced by Silastic capsules implanted in animals of the ovariectomized, hormone-treated group were similar to natural levels of those hormones induced during pregnancy. Quantitative receptor autoradiography and radioimmunoassay were used to determine [3H]naloxone binding density and immunoreactive β-endorphin content, respectively, in the preoptic area of the hypothalamus. Both opiate receptor binding density and β-endorphin content in the preoptic area varied in the same direction in all experimental groups. The highest levels of both were observed during pregnancy and the lowest levels during lactation. Ovariectomy without subsequent hormone treatment produced intermediate levels of both opiate receptor and β-endorphin. Ovariectomy with experimentally-induced estradiol and progesterone levels similar to those of pregnancy produced opiate receptor density and β-endorphin content similar to those observed in pregnant animals. These data suggest that gonadal steroids are capable of altering function of the endogenous opiate system in the preoptic area. Moreover, preoptic area levels of opioids and opiate receptors are normally elevated during pregnancy and reduced during lactation. Since opiates are known to disrupt ongoing maternal behavior, a reduction of preoptic opiate function during lactation may berequired to promote normal maternal behavior. The specific preoptic region involved in opiate regulation of maternal behavior may be illustrated by the zone of opiate receptor alteration observed herein.
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Preoptic area opiate receptor density was measured by quantitative autoradiography using [3H]naloxone in female rats during their first and second pregnancies and lactations and in a separate group of ovariectomized, nulliparous animals. Opiate receptor density in the medial preoptic area (MPOA) was elevated on day 12 of gestation in both primigravid and multigravid rats when compared with ovariectomized subjects. MPOA receptor density was reduced in primaparous mothers on day 5of lactation relative to pregnancy. In contrast, receptor density in the MPOA did not decline in multiparous (second lactation) rats relative to pregnancy levels. Opiate receptor density was significantly higher on day 5 of lactation in multiparous than in primiparous mothers. No difference in receptor density was detected in the adjacent lateral preoptic area among the treatment groups. An examination of hormone titers revealed that basal prolactin levels were significantly higher in primigravid than multigravid rats, and that during lactation prolactin titers were negatively correlated with MPOA opiate receptor density in the primiparous mothers. The data demonstrate that multiple pregnancies and lactations result in changes of MPOA opiate receptor density and of circulating hormone levels. The findings are discussed in terms of the concurrent changes in neural opiate sensitivity associated with multiparity.
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A number of hypotheses have been proposed for the evolution of sex differences in spatial ability. Two of these hypotheses assume a sex-based division of labor in foraging during human evolutionary history, three propose sexual selection for spatial ability, and two suggest that human life history has imposed sex-specific selection on spatial abilities. We derive predictions from each of these models and test the predictions against recent data on the effects of hormones on spatial ability across the lifespan. Sexual selection for increased range size in males might be the evolutionary origin of the enhancing effects of testosterone on spatial ability, while the benefits of reduced mobility in women at different stages of reproduction could be the origin of the inhibitory effects of oestrogen on spatial ability.
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The effects of chronic estrogen treatment on radial arm maze performance and on levels of central monoaminergic and amino acid neurotransmitters were examined in ovariectomized (Ovx) rats. In an eight arms baited paradigm, choice accuracy was enhanced following 12 days but not 3 days of treatment. In addition, performance during acquisition of the eight