Effects of chronic maternal stress on hypothalamo–pituitary–adrenal (HPA) function and behavior: No reversal by environmental enrichment

Maternal stress during pregnancy is linked to increased risk for impaired behavioral and emotional development and affective disorders in children. In animal models, acute periods of prenatal or postnatal stress have profound effects on HPA function and behavior in adult offspring. However, few animal studies have determined the impact of chronic exposure to stress throughout the perinatal period. The objective of this study was to determine the effects of chronic maternal stress (CMS) during the 2nd half of pregnancy and nursing on HPA function, locomotor behavior and prepulse inhibition in adult guinea pig offspring, as well as to determine whether environmental enrichment (EE) could reverse the effects of CMS. Guinea pigs were exposed to a random combination of variable stressors every other day over the 2nd half of gestation and from postnatal day (pnd) 1 until weaning (pnd25). Following weaning, offspring were housed in either standard conditions or EE. In both adult male and female offspring, there was no effect of CMS on basal or activated HPA function. CMS significantly increased locomotor activity in an open-field in male offspring, though no effect was observed in females. In female offspring, CMS disrupted PPI; however there was no effect on male PPI. EE had a number of effects on HPA function and behavior but in most cases these were independent of the influence of CMS. EE significantly elevated basal cortisol levels in male offspring at pnd70, whereas in female offspring, EE interacted with CMS to elevate basal cortisol levels from pnd35 to pnd70. In female offspring, EE decreased locomotor activity. In males, EE enhanced PPI; however in female offspring EE disrupted PPI. In conclusion, while CMS had minimal effects on HPA function, there were significant long-term sex-specific effects on behavior. EE did not reverse the effects observed as a result of CMS, but rather modified HPA function and behavior independently of CMS. Further, there was significant interaction of CMS with EE that resulted in elevation of basal HPA function in female offspring. These data, combined with previous studies from our laboratory, suggest that acute phases of maternal stress in late pregnancy may have greater long-term effects on HPA function and related behaviors than prolonged chronic maternal stress.     

Chronic maternal stress affects growth, behaviour and hypothalamo-pituitary-adrenal function in juvenile offspring

Maternal stress during pregnancy, particularly that combined with low socioeconomic status (SES), has been linked to an increased risk for impaired behavioural and emotional development and affective disorders in children. In animal models, acute periods of prenatal stress have profound effects on hypothalamo-pituitary-adrenal (HPA) function and behaviour. However, few studies have determined the impact of chronic exposure to stress in animal models. The objective of this study was to determine the effects of chronic maternal stress (CMS) during the 2nd half of pregnancy and nursing on growth, locomotor behaviour and HPA axis function in juvenile guinea pig offspring. Pregnant guinea pigs were exposed to a random combination of variable stressors every other day over the 2nd half of gestation and from postnatal day (pnd) 1 until weaning (pnd25). CMS mothers displayed increased basal salivary cortisol levels in the later stages of pregnancy compared to control mothers (p < 0.05). The male offspring of CMS mothers had a lower bodyweight, which was maintained to weaning (p < 0.01). In open-field testing, CMS male offspring showed a decrease in activity compared to controls (p < 0.05). There was no effect of CMS on bodyweight or activity in female offspring. In contrast, both male and female offspring born to CMS mothers displayed increased (p < 0.05) basal salivary cortisol at pnd25, but a blunted adrenocortical response to exposure to the novel open-field enclosure. In conclusion, CMS leads to modification of growth trajectory, locomotor activity and adrenocortical responses to stress in juvenile offspring. Further, males appear considerably more vulnerable to these effects than females.     

Maternal glucocorticoid deficit affects hypothalamic-pituitary-adrenal function and behavior of rat offspring

Detrimental consequences of prenatal stress include increased hypothalamic-pituitary-adrenal (HPA) function, anxiety and depression-like behavior in adult offspring. To identify the role of maternal corticosterone milieu in the fetal programming of adult function, we measured these same behavioral and hormonal endpoints after maternal adrenalectomy (ADX) and replacement with normal or moderately high levels of corticosterone (CORT). Adult male and female offspring exhibited differing HPA responses to maternal ADX. In female offspring of ADX mothers, exaggerated plasma ACTH stress responses were reversed by the higher, but not the lower, dose of maternal CORT. In contrast, male offspring of both ADX and ADX dams with higher CORT replacement showed exaggerated ACTH stress responses. Hypothalamic glucocorticoid receptor (GR) expression was decreased in these latter groups, while hippocampal GR increased only in the ADX offspring. Activity of young offspring of ADX dams replaced with the higher dose of CORT decreased in the open field test of exploration/anxiety, while immobility behavior of adult offspring in the forced swim test of depression increased following maternal ADX or higher levels of CORT replacement. Interestingly, for some measures, none or moderately high CORT replacement resulted in similar deficits in this study. These findings are in accord with consequences of prenatal stress or prenatal dexamethasone exposure, suggesting that a common mechanism may underlie the effects of too low or too high maternal glucocorticoids on adult HPA function and behavior.     

根田鼠母体捕食应激对其子代运动及探究行为的作用

本文研究了根田鼠母体捕食应激对其子代运动及探究行为的作用。母体自妊娠中期至分娩期间,每天被短暂且重复地暴露给艾鼬。分娩后,对母体及其子代正常饲养。在子代性成熟后,分别测定其运动和探究行为。母体捕食应激显著降低子代的运动时间和频率。在探究行为中,母体捕食应激子代的探究潜伏期和探究时间均显著大于对照子代;其次,母体捕食应激雌性子代的探究次数显著小于对照。另外,个体的运动水平以及探究潜伏期和探究次数均存在性别差异。本研究结果表明,田鼠类母体捕食应激对其子代运动和探究行为有显著的抑制作用,由此可能对子代适合度,乃至种群波动产生负效应。     

Behavioral activity and stress reaction of the pituitary-adrenocortical axis in rat with prenatal inhibition of testosterone metabolism

The effects of maternal administration of the aromatase inhibitor, 1,4,6-androstatrien-3,17-dione (ATD), during the last week of gestation on stress reaction of the hypothalamic-pituitary-adrenal axis (HPA) and behavior in a novel environment (open field) and the anxiety level in the elevated plusmaze, were studied in male and female adult offspring. The results showed that parental inhibition of brain testosterone metabolism decreases the basic level of corticosterone in male rats and prolongs hormonal stress reaction of the HPA axis in both sexes. Prenatally treated rats demonstrated significant elevation of the anxiety level and emotionality. There was no sexual dimorphism in behavioral response to a novel environment such as locomotor activity, the time of immobilization, the total duration of grooming reaction, and the anxiety level, between control male and treated female rats. These data suggest a prenatal inhibition of the brain testosterone metabolism after the stress reaction of HPA axis and formation of sexual dimorphism in the anxiety and behavioral response to a novel environment in adulthood.     

Influence of prenatal stress on the rat hypothalamic-pituitary-adrenal axis activity: the role of the brain glycocorticoid receptors

The effects of prenatal stress on the hypothalamic-pituitary-adrenal (HPA) axis activity and brain glycocorticoid receptors were studied in neonatal male and female offspring, as well as the influence of neonatal glycocorticoid receptors blockade on hormonal stress reactivity of adult rats. The results showed that there were sexual differences in plasma corticosterone level and corticosteroid binding in the cortex and hypothalamus of 5-day old control rats. Prenatal stress increased basal level of corticosterone in female rats, decreased corticosterone binding in hypothalamus and hippocampus of male and female rats, and increased corticosteroid receptor level in the male cortex. Neonatal administration of glycocorticoid receptor antagonist did not change plasma corticosterone level in 5-day old rats, but prolonged hormonal stress response of the HPA axis in adult male rats and increased hormonal stress response in female ones. The character of the IIPA axis activity of male and female rats with neonatal blockade of glycocorticoid receptors correspond to hormonal stress response of prenatal stressed rats. These data suggest that change of brain glycocorticoid receptors function in neonatal period of development might be one of the mechanisms of prenatal stress influence on the HPA axis activity in the adulthood.     

Gender-specific effects of prenatal stress on emotional reactivity and stress physiology of goat kids

The aims of this study were to investigate the effects of maternal stress during pregnancy on the emotional reactivity, the hypothalamo-pituitary-adrenocortical (HPA) axis, and the sympatho-adrenomedullary (SAM) system of goat offspring according to their gender, and to investigate the role of maternal cortisol in prenatal stress effects. Goats were exposed to ten transports in isolation or ten ACTH injections (0.125 IU/kg body weight) during the last third of pregnancy. Control goats remained undisturbed. No effect of repeated transport during the last third of pregnancy was found on basal cortisol concentrations of the offspring. However, an increase in phenylethanolamine N-methyl transferase activity in the adrenals was observed in prenatally stressed kids compared to control kids (P = 0.031). In the presence of novelty, prenatally stressed female kids were more active (P = 0.049) than control females; they also showed more signs of arousal (P = 0.039) and tended to explore more of their environment (P = 0.053) in reaction to a startling stimulus. On the contrary, prenatally stressed male kids tended to be less active (P = 0.051) than control male kids but showed more signs of distress (P = 0.047) in the presence of novelty. Intermediate effects were found on the emotional reactivity to novelty of kids born from dams given injections of ACTH. In conclusion, transport stress in pregnant goats affects the sympatho-adrenomedullary system and the emotional reactivity of their offspring in a gender-specific manner. Moreover, the effects of prenatal transport and ACTH injections showed some similarities but differed in some critical details.     

Effects of maternal corticosterone and stress on behavioral and hormonal indices of formalin pain in male and female offspring of different ages

In previous studies, we showed for the first time that prenatal stress in rats produces long-term alterations of formalin-induced pain behavior that are dependent on age and sex, and we demonstrated an important role of the serotonergic system in mechanisms of prenatal stress (Butkevich, I.P. and Vershinina, E.A., 2001; Butkevich, I.P. and Vershinina, E.A., 2003; Butkevich, I.P., Mikhailenko, V.A., Vershinina, E.A., Khozhai, L.I., Grigorev, I.P., Otellin, V.A., 2005; Butkevich, I.P., Mikhailenko, V.A., Khozhai, L.I., Otellin, V.A., 2006). In the present study, we focus on the influence of the maternal corticosterone milieu and its role in the effects of stress during pregnancy on formalin-induced pain and the corticosterone response to it in male and female offspring of different ages. For this purpose, we used adrenalectomy (AD) in female rats 3-4 weeks before mating (as distinct from AD typically performed at the beginning of pregnancy). Since AD is considered a reliable method to treat hypercortisolism, researches on the effects of long-term AD in dams on the systems responsible for adaptive behavior in offspring are important (such studies are not described in the literature). The results demonstrate that the differences in the corticosterone response to injection of formalin and saline are obvious in 90-day-old (adult) female offspring but masked in 25-day-old ones. AD promoted the corticosterone response to formalin-induced pain but not to injection of saline in prenatally non-stressed female offspring of both ages. Prenatal stress canceled the differences in corticosterone response to injection of formalin and saline in 25-day-old offspring of AD dams and in adult offspring of sham-operated (SH) dams but caused similar differences in adult offspring of AD dams. Sex differences were found in basal corticosterone levels in AD prenatally stressed rats of both age groups, with a higher level in females, and in the corticosterone response to formalin-induced pain in the adult rats of all groups investigated, with higher corticosterone levels in females. In regard to pain behavior, AD induced significant changes in flexing + shaking in prenatally non-stressed adult offspring and canceled the differences in this behavior between non-stressed and stressed 25-day-old offspring. There were sex differences in pain behavior of the adult rats: greater flexing + shaking in AD non-stressed males but in SH non-stressed females; greater licking in prenatally-stressed AD and SH females. These results indicate that the long-term influences of maternal corticosterone on formalin-induced pain and the corticosterone response to it are determined by the sex and age of the offspring and suggest that other mechanisms, including serotonergic ones revealed in our previous studies, are involved in the effects of prenatal stress on inflammatory pain behavior.     

Transgenerational effects of social stress on social behavior,corticosterone, oxytocin,and prolactin in rats

Social stressors such as depressed maternal care and family conflict are robust challenges which can have long-term physiological and behavioral effects on offspring and future generations. The current study investigates the transgenerational effects of an ethologically relevant chronic social stress on the behavior and endocrinology of juvenile and adult rats. Exposure to chronic social stress during lactation impairs maternal care in F0 lactating dams and the maternal care of the F1 offspring of those stressed F0 dams. The overall hypothesis was that the male and female F2 offspring of stressed F1 dams would display decreased social behavior as both juveniles and adults and that these behavioral effects would be accompanied by changes in plasma corticosterone, prolactin, and oxytocin. Both the female and male F2 offspring of dams exposed to chronic social stress displayed decreased social behavior as juveniles and adults, and these behavioral effects were accompanied by decreases in basal concentrations of corticosterone in both sexes, as well as elevated juvenile oxytocin and decreased adult prolactin in the female offspring. The data support the conclusion that social stress has transgenerational effects on the social behavior of the female and male offspring which are mediated by changes in the hypothalamic–pituitary–adrenal axis and hypothalamic–pituitary–gonadal axis. Social stress models are valuable resources in the study of the transgenerational effects of stress on the behavioral endocrinology of disorders such as depression, anxiety, autism, and other disorders involving disrupted social behavior.     

Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function

Alcohol abuse is known to result in clinical abnormalities of endocrine function and neuroendocrine regulation. However, most studies have been conducted on males. Only recently have studies begun to investigate the influence of alcohol on endocrine function in females and, more specifically, endocrine function during pregnancy. Alcohol-induced endocrine imbalances may contribute to the etiology of fetal alcohol syndrome. Alcohol crosses the placenta and can directly affect developing fetal cells and tissues. Alcohol-induced changes in maternal endocrine function can disrupt maternal-fetal hormonal interactions and affect the female's ability to maintain a successful pregnancy, thus indirectly affecting the fetus. In this review, we focus on the adverse effects of prenatal alcohol exposure on neuroendocrine and immune function, with particular emphasis on the hypothalamic-pituitary-adrenal (HPA) axis and the concept of fetal programming. The HPA axis is highly susceptible to programming during fetal development. Early environmental experiences, including exposure to alcohol, can reprogram the HPA axis such that HPA tone is increased throughout life. We present data that demonstrate that maternal alcohol consumption increases HPA activity in both the maternal female and the offspring. Increased exposure to endogenous glucocorticoids throughout the lifespan can alter behavioral and physiologic responsiveness and increase vulnerability to illnesses or disorders later in life. Alterations in immune function may be one of the long-term consequences of fetal HPA programming. We discuss studies that demonstrate the adverse effects of alcohol on immune competence and the increased vulnerability of ethanol-exposed offspring to the immunosuppressive effects of stress. Fetal programming of HPA activity may underlie some of the long-term behavioral, cognitive, and immune deficits that are observed following prenatal alcohol exposure.     

Prenatal stress and gender role behavior in girls and boys: a longitudinal,population study

Prenatal stress influences neural and behavioral sexual differentiation in rodents. Male offspring of stressed pregnancies show reduced masculine-typical characteristics and increased feminine-typical characteristics, whereas female offspring show the opposite pattern, reduced feminine-typical and increased masculine-typical characteristics. These outcomes resemble those seen following manipulations of gonadal hormones and are thought to occur because stress influences these hormones during critical periods of development. Research on prenatal stress and human sexual differentiation has produced inconsistent results, perhaps because studies have used small samples and assessed prenatal stress retrospectively. We related maternal self-reports of prenatal stress to childhood gender role behavior in a prospective, population study of 13,998 pregnancies resulting in 14,138 offspring. Neither stress reported during the first 18 weeks of pregnancy nor stress reported from week 19 of pregnancy to week 8 postnatal related to gender role behavior in male offspring at the age of 42 months. In female offspring, maternal reports of stress during both periods showed only small correlations with masculine-typical behavior. Although this relationship remained significant when other factors that related to stress were controlled, these other factors made larger contributions to girls' gender role behavior than did prenatal stress. In addition, in both boys and girls, older male or female siblings, parental adherence to traditional sex roles, maternal use of tobacco or alcohol during pregnancy, and maternal education all related significantly to gender role behavior. Our results suggest that prenatal stress does not influence the development of gender role behavior in boys and appears to have relatively little, if any, influence on gender role behavior in girls.     

Prenatal Restraint Stress is Associated with Demethylation of Corticotrophin Releasing Hormone (CRH) Promoter and Enhances CRH Transcriptional Responses to Stress in Adolescent Rats

Maternal stress can disturb normal fetal neurodevelopmental progress, and lead to negative behavioral and neuroendocrine consequences for the offspring. These effects may be related to alterations in the hypothalamic–pituitary–adrenal (HPA) axis. Early life events disrupting the function of the HPA axis may be associated with epigenetic modification. This study investigated the effect of maternal stress on the methylation rate of the corticotrophin-releasing hormone (CRH) promoter and HPA axis response to acute stress in the adolescent offspring of Sprague–Dawley rats. Pregnant dams were randomly assigned to two groups: restraint stress group and normal control group. Adolescent male and female offspring were used from each group. The results showed that prenatal stress is associated with the demethylation of the CRH promoter, and leads to anxiety-like behaviors in adolescent life stages, as well as hyper-responsiveness of the HPA axis. Together, these results imply that prenatal stress alters the normal HPA function, which may be via the epigenetic mechanism.     

Effect of predator-induced maternal stress during gestation on growth in root volesMicrotus oeconomus

We studied the effect of maternal stress evoked by a severe stressor from the cues of predation risk during gestation on the growth of offspring in root volesMicrotus oeconomus Pallas, 1776. Body mass of both male and female offspring was significantly reduced in the period from birth to weaning. Females showed compensatory growth after weaning, whereas males maintained low body mass at weaning into adulthood. Maternal stress led to an elevated plasma corticosterone level in male offspring, but did not affect that of female offspring. Corticosterone levels remained elevated in males from stressed dams into adulthood. Increased levels of plasma corticosterone may have led to the inhibition of pituitary growth hormone and a chronically abnormal energy mobilization, considering the greater energy and metabolic requirements of male offspring, this may account for the sex-specific differences in compensatory growth. We suggest that in the high stress situation, endocrine-based sex-biased effects of maternal stress as a primary factor can lead to long-term physical and ecological consequences for male offspring.     

Responses of the hypothalamic-pituitary-adrenal axis to noradrenergic and hormonal stimulation in prenatally stressed rats

We studied the effects of maternal stress (the so-called prenatal stress, PS, provided by immobilization of pregnant female Wistar rats for 1 h daily during the 15–21st gestational days) on the corticosterone response in the blood plasma evoked by infusion of 10 μg noradrenaline bitartrate into the III cerebral ventricle or by injection of β-1-24-corticotropin in 3-month-old male and female offspring. The animals were bearing an intracerebroventricular stainless steel guide cannula implanted eight to nine days before the experiment, and a Silastic catheter inserted into the external jugular vein 24 h prior to the experiment. Blood samples were periodically taken from conscious unrestrained rats (before and then 30, 60 and 90 or 120 min after noradrenaline or corticotropin challenge). In the male offspring PS augmented and prolonged an increase in the plasma corticosterone level resulting from adrenergic stimulation of the hypothalamus, as compared with that in non-stressed animals. In prenatally stressed female offspring tested in diestrus, there was no response of the hypothalamic-pituitary-adrenal (HPA) axis to intracerebroventricular noradrenaline stimulation, in contrast to what was observed in the control. Prenatal stress did not modify the adrenal cortex responsiveness to corticotropin either in male or in female offspring. The results demonstrate differential effects of PS on the adrenergic activation of the HPA axis in males and females. A decrease in the acute HPA stress-responsiveness in prenatally stressed male rats, which was demonstrated in an earlier study, and the maintenance or even enhancement of this effect in prenatally stressed females are not likely to be connected with the state of hypothalamic adrenergic reactivity.     

Behavioral despair in mice after prenatal stress

Maternal stress during pregnancy produced behavioral alterations in both sexes with regard to sexual behavior, aggressive, maternal, lateralization and depression. In the present paper, sex differences for depression in mice was studied. No sex differences between female and male mice groups were observed either in swimming-induced immobility or in the open-field test (ambulation, rearing and boluses). Prenatal stress produced: 1) an increase of immobility time in female mice for swimming-induced immobility, but not in male mice; 2) an increase of ambulation in female mice for open-field test, but not in male mice; 3) there were no significant differences in rearing and boluses between stress and control groups either for female or male mice. Prenatal stress increases the risk of depression and locomotor activity in adult female mice.     

根田鼠母体捕食应激效应与Trivers-Willard 模型的关系

本研究了根田鼠母体捕食应激对其子代出生、断乳和成体体重、窝性比及死亡率的作用,检验Trivers—Willard模型的2个前提条件、母体应激激素在母体投资中的作用,以及母体捕食应激效应与该模型的关系。将妊娠根田鼠母体暴露于其捕食艾鼬,母体应激子代的出生和断乳体重均显降低;到成体,雄性体重有此效应,而雌性体重则接近对照。出生窝性比无变化,但成体窝性比向雌性偏斜。不同年龄阶段的死亡率无显变化,但累计死亡率明显增大。处理雄性子代在断乳和成体时的皮质酮含量显增高,而雌性子代则无显变化,从而验证了Trivers-Willard模型的2个前提条件,提出应激母体激素参与母体对子代的投资观点,并认为,母体捕食应激使根田鼠子代成体窝性比向雌性偏斜的生理投资符合进化稳定对策。     

Deprivation of maternal care has long-lasting consequences for the hypothalamic-pituitary-adrenal axis of zebra finches

Early-life stress caused by the deprivation of maternal care has been shown to have long-lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis in offspring of uniparental mammalian species. We asked if deprivation of maternal care in biparental species alters stress responsiveness of offspring, using a biparental avian species--the zebra finch, Taeniopygia guttata. In our experiment, one group of birds was raised by both male and female parents (control), and another was raised by males alone (maternally deprived). During adulthood, offspring of both groups were subjected to two stressors (restraint and isolation), and corticosterone concentrations were measured. Additionally, we measured baseline levels of the two corticosteroid receptors--glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)--in the hippocampus, hypothalamus and cerebellum. Our results suggest that maternally deprived offspring are hyper-responsive to isolation in comparison with controls. Furthermore, mRNA levels of both GR and MR receptors are altered in maternally deprived offspring in comparison with controls. Thus, absence of maternal care has lasting consequences for HPA function in a biparental species where paternal care is available.     

Paternal behavior influences development of aggression and vasopressin expression in male California mouse offspring

Parental care has been demonstrated to have important effects on offspring behavioral development. California mice (Peromyscus californicus) are biparental, and correlational evidence suggests that pup retrieving by fathers has important effects on the development of aggressive behavior and extra-hypothalamic vasopressin systems. We tested whether retrievals affected these systems by manipulating paternal retrieval behavior between day 15 and 21 postpartum. Licking and grooming behavior affect behavioral development in rats, so we also experimentally reduced huddling and grooming behavior by castrating a subset of fathers. Experimentally increasing the frequency of paternal pup retrieving behavior decreased attack latency in resident-intruder in both male and female adult offspring, whereas experimental reduction of huddling and grooming had no effect. In a separate group of male offspring, we examined vasopressin immunoreactivity (AVP-ir) in two regions of the posterior bed nucleus of the stria terminalis (BNST): the dorsal fiber tracts (dBNST) and the ventral cell body-containing region (vBNST). Experimentally increasing retrievals led to an apparent shift in AVP-ir distribution. Specifically, offspring from the high retrieval group had more AVP-ir than offspring from the sham retrieval group in the dBNST, whereas the opposite was observed in the vBNST. Experimental reduction of paternal grooming was associated with increased AVP-ir in the paraventricular nucleus and also increased corticosterone and progesterone, similar to observed effects of maternal grooming on HPA function. This study provides further evidence that paternal behavior influences the development of aggression and associated neural substrates.     

Prenatal stress alters circadian activity of hypothalamo-pituitary-adrenal axis and hippocampal corticosteroid receptors in adult rats of both gender.

Prenatal stress impairs activity of the hypothalamo-pituitary-adrenal (HPA) axis in response to stress in adult offspring. So far, very few data are available on the effects of prenatal stress on circadian functioning of the HPA axis. Here, we studied the effects of prenatal stress on the circadian rhythm of corticosterone secretion in male and female adult rats. To evaluate the effects of prenatal stress on various regulatory components of corticosterone secretion, we also assessed the diurnal fluctuation of adrenocorticotropin, total and free corticosterone levels, and hippocampal corticosteroid receptors. Finally, in the search of possible maternal factors, we studied the effects of repeated restraint stress on the pattern of corticosterone secretion in pregnant female rats. Results demonstrate that prenatal stress induced higher levels of total and free corticosterone secretion at the end of the light period in both males and females, and hypercorticism over the entire diurnal cycle in females. No diurnal fluctuation of adrenocorticotropin was observed in any group studied. The effects of prenatal stress on corticosterone secretion could be mediated, at least in part, by a reduction in corticosteroid receptors at specific times of day. Results also show that prepartal stress alters the pattern of corticosterone secretion in pregnant females. Those data indicate that prenatally stressed rats exhibit an altered temporal functioning of the HPA axis, which, taken together with their abnormal response to stress, reinforces the idea of a general homeostatic dysfunction in those animals.     

Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations

The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2–14, male Wistar rats (n?=?8 per group) were daily separated from their mothers for a period of either 180?min (long maternal separation; LMS) or 10?min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors.