Stressed Dams Research Articles

Strain dependent effects of prenatal stress on gene expression in the rat hippocampus

Multiple animal models have been developed to recapitulate phenotypes of the human disease, schizophrenia. A model that simulates many of the cognitive and sensory deficits of the disorder is the use of random variable prenatal stress (PS) in the rat. These deficits suggest a molecular origin in the hippocampus, a brain region that plays a role in the regulation of stress. To study both hippocampal gene expression changes in offspring of prenatally stressed dams and to address genetic variability, we used a random array of prenatal stressors in three different rat strains with diverse responses to stress: Fischer, Sprague–Dawley, and Lewis rats. Candidate genes involved in stress, schizophrenia, cognition, neurotrophic effects, and immunity were selected for assessment by real-time quantitative PCR under resting conditions and following a brief exposure to restraint stress. PS resulted in significant differences in gene expression in the offspring that were strain dependent. mRNA expression for the N-methyl- d-aspartate receptor subtype 2B ( Grin2b) was increased, and tumor necrosis factor-alpha ( Tnfα) transcript was decreased in PS Sprague–Dawley and Lewis rats, but not in the Fischer rats. Expression of brain-derived neurotrophic factor ( Bdnf) mRNA in the hippocampus was increased after an acute stress in all controls of each strain, yet a decrease was seen after acute stress in the PS Sprague–Dawley and Lewis rats. Expression of the glucocorticoid receptor ( Nr3c1) was decreased in the Fischer strain when compared to Lewis or Sprague–Dawley rats, though the Fischer rats had markedly higher α7 nicotinic receptor ( Chrna7) expression. The expression differences seen in these animals may be important elements of the phenotypic differences seen due to PS and genetic background.

Towards a better understanding of maternal mental health: the effect of chronic stress on peripartum adaptations

Maternal adaptations, such as decreased anxiety and attenuated stress-responsiveness, are necessary to enable successful post-natal protection and nurturance of the offspring. However, there is growing evidence that they are also required to protect the mental health of the mother, and that exposure to stress during pregnancy may attenuate such adaptations. Therefore, we developed a chronic pregnancy stress paradigm, combining social instability with restraint stress, and examined its impact on numerous peripartum adaptations under basal or chronic imipramine (10mg/kg/d) conditions. To determine whether the alterations where specific to the peripartum period we included virgins as an additional control. We validated the stress procedure by demonstrating decreased body weight gain and increased adrenal weight in stressed dams, and virgins, relative to their respective unstressed controls. Stress exposure prevented a number of peripartum adaptations, including basal plasma hyper-corticosterone levels, increased oxytocin mRNA expression in the hypothalamic paraventricular nucleus (PVN) and anxiolysis. However, none of these parameters were affected in virgins. Maternal behaviour was also elevated in the stressed group compared with controls. While stress exposure did not alter depression-related behaviour in virgins, it reversed the response to acute imipramine treatment in lactation. Interestingly, while the behavioural consequences of stress exposure could be reversed by chronic imipramine treatment, the physiological parameters persisted. Thus, this chronic psychosocial stress paradigm has revealed important consequences of pregnancy stress, which represent novel systems to explore in a clinical environment.

“Green odor” inhalation by stressed rat dams reduces behavioral and neuroendocrine signs of prenatal stress in the offspring

Chronic maternal stress during pregnancy results in the “prenatally stressed” offspring displaying behavioral and neuroendocrine alterations that persist into adulthood. We investigated how inhalation of green odor (a mixture of equal amounts of trans-2-hexenal and cis-3-hexenol) by stressed dams might alter certain indices of prenatal stress in their offspring. These indices were depression-like behavior (increased immobility time in the forced-swim test) and acute restraint stress-induced changes in hypothalamo–pituitary–adrenocortical (HPA) axis activity [plasma corticosterone (CORT) and ACTH levels and the number of Fos-immunoreactive cells in the hypothalamic paraventricular nucleus (an index of neuronal activity)]. Pregnant rats were exposed to restraint stress for 60 min/day for 10 days (gestational days 10–19). The prenatally stressed offspring exhibited significant increases in depression-like behavior and in restraint stress-induced ACTH, CORT, and Fos responses, unless their dam had been exposed to green odor. The behavioral effect of the odor was also seen in offspring that were fostered by unstressed dams. The results obtained in the dams themselves were as follows. In vehicle-exposed stressed dams, but not in green odor-exposed ones, total body and adrenal weights were significantly decreased or increased, respectively. Depression-like behavior was not observed in the vehicle-exposed stressed dams themselves. Green odor inhalation prevented the impairment of maternal behavior induced by restraint stress. Thus, exposure of dams to stress may affect both the fetal brain and fetal HPA axis, and also maternal behavior, leading to altered behavioral and neuroendocrine responses in the offspring. Such effects may be prevented by the stressed dams inhaling green odor.

The sensitive hare: sublethal effects of predator stress on reproduction in snowshoe hares

1. Prey responses to high predation risk can be morphological or behavioural and ultimately come at the cost of survival, growth, body condition, or reproduction. These sub-lethal predator effects have been shown to be mediated by physiological stress. We tested the hypothesis that elevated glucocorticoid concentrations directly cause a decline in reproduction in individual free-ranging female snowshoe hares, Lepus americanus. We measured the cortisol concentration from each dam (using a faecal analysis enzyme immunoassay) and her reproductive output (litter size, offspring birth mass, offspring right hind foot (RHF) length) 30 h after birth. 2. In a natural monitoring study, we monitored hares during the first and second litter from the population peak (2006) to the second year of the decline (2008). We found that faecal cortisol metabolite (FCM) concentration in dams decreased 52% from the first to the second litter. From the first to the second litter, litter size increased 122%, offspring body mass increased 130%, and offspring RHF length increased 112%. Dam FCM concentrations were inversely related to litter size (r(2) = 0.19), to offspring birth mass (r(2) = 0.32), and to offspring RHF length (r(2) = 0.64). 3. In an experimental manipulation, we assigned wild-caught, pregnant hares to a control and a stressed group and held them in pens. Hares in the stressed group were exposed to a dog 1-2 min every other day before parturition to simulate high predation risk. At parturition, unsuccessful-stressed dams (those that failed to give birth to live young) and stressed dams had 837% and 214%, respectively, higher FCM concentrations than control dams. Of those females that gave birth, litter size was similar between control and stressed dams. However, offspring from stressed dams were 37% lighter and 16% smaller than offspring from control dams. Increasing FCM concentration in dams caused the decline of offspring body mass (r(2) = 0.57) and RHF (r(2) = 0.52). 4. This is the first study in a free-ranging population of mammals to show that elevated, predator-induced, glucocorticoid concentrations in individual dams caused a decline in their reproductive output measured both by number and quality of offspring. Thus, we provide evidence that any stressor, not just predation, which increases glucocorticoid concentrations will result in a decrease in reproductive output.

Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk

To understand the pathophysiology of neuropsychiatric disorders such as schizophrenia requires consideration of multiple genetic and non-genetic factors. However, very little is known about the consequences of combining models of synaptic dysfunction with controlled environmental manipulations. Therefore, to generate new insights into gene–environment interactions and complex behaviour, we examined the influence of variable prenatal stress (PNS) on two mouse lines with mutations in synaptosomal-associated protein of 25 kDa (Snap-25): the blind-drunk (Bdr) point mutant and heterozygous Snap-25 knockout mice. Neonatal development was analysed in addition to an assessment of adult behavioural phenotypes relevant to the psychotic, cognitive and negative aspects of schizophrenia. These data show that PNS influenced specific anxiety-related behaviour in all animals. In addition, sensorimotor gating deficits previously noted in Bdr mutants were markedly enhanced by PNS; significantly, these effects could be reversed with the application of anti-psychotic drugs. Moreover, social interaction abnormalities were observed only in Bdr animals from stressed dams but not in wild-type littermates or mutants from non-stressed mothers. These results show for the first time that combining a synaptic mouse point mutant with a controlled prenatal stressor paradigm produces both modified and previously unseen phenotypes, generating new insights into the interactions between genetics and the environment relevant to the study of psychiatric disease.

Altered functional development of the blood–brain barrier after early life stress in the rat

This study investigated the effect of early life stress on blood–brain barrier functional development in an altricial mammal, the Wistar rat. Forced swimming between gestational days 10–20 was used as a stress procedure in pregnant rats. After delivery, half of the control litters underwent 180 min maternal separation from postnatal day 2–20. Controls were kept without any stress manipulations. At sacrifice between postnatal days 1–30 subjects were given intracardiac Evans blue or the lectin wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Evans blue-stained brain slices were photographed and optical density quantified. WGA-HRP stained brains were processed for ultrastructural analysis. Plasma corticosterone at embryonic day 20 and postnatal days 1, 10, 20 and 30 was quantified by radioimmunoassay. At postnatal day 10, postnatal stress increased Evans blue entry to the neocortex, hippocampus, diencephalon, basal ganglia, olfactory bulb, brain stem, cerebellum, and spinal cord. At postnatal day 20, prenatal stress increased Evans blue concentration in the same regions as those affected after postnatal stress. Between postnatal days 10–20, both stress groups showed increased WGA-HRP caveolae-mediated transport in the hippocampal capillaries. By postnatal day 30, the blood–brain barrier was functionally mature in both control and stressed pups. Plasma corticosterone concentration was higher in pregnant stressed dams as compared to controls. Postnatal stress increased plasma corticosterone at postnatal days 10 and 20. The findings suggest that chronic perinatal stress alters blood–brain barrier functional development by increasing caveolae-mediated transport in brain endothelial cells.

Maternal stress and development of atherosclerosis in the adult apolipoprotein E-deficient mouse offspring

Stress is a risk factor for cardiovascular disease, such as atherosclerosis. Stress during pregnancy (maternal stress) may have long-term consequences for the health of the offspring. However, it is not known whether maternal stress affects the offspring's predisposition to develop atherosclerosis. Atherosclerosis is often related to vascular endothelial dysfunction. We hypothesized that maternal stress affects vascular endothelial function and accelerates development of atherosclerosis in offspring of apolipoprotein E-deficient mice, a model commonly used for atherosclerosis research. Stress was induced by restraining dams in small cylinders for five consecutive days (2 h/day) beginning on gestational day 8 +/- 0.5. Vascular function and development of atherosclerosis in the aorta were determined in male and female offspring at 11-15 wk of age (with early lesions) and at 22-26 wk of age (with established lesions). Endothelium-dependent vasorelaxation was determined using methacholine (0.0001-10 micromol/l) in the absence or presence of the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester hydrochloride (l-NAME; 100 micromol/l). Male offspring (11-15 wk old) from stressed dams were less dependent on nitric oxide for relaxation compared with controls (l-NAME inhibition: 38 +/- 10 vs. 69 +/- 6%, P < 0.05). Atherosclerotic lesion area was larger in male and female 25- to 26-wk-old offspring from stressed dams compared with corresponding controls [median (interquartile range): males: 6.8 (5.4-7.7) vs. 5.1 (4.4-5.5), P < 0.05, females: 10.0 (8.9-10.9) vs. 7.0 (4.7-8.7), P < 0.05]. In conclusion, maternal stress renders the apolipoprotein E-deficient offspring more susceptible to develop atherosclerosis.

Increased formalin-induced pain and expression of fos neurons in the lumbar spinal cord of prenatally stressed infant rats

When pregnant dams are stressed, there is a resultant alteration in brain development and behavior in their offspring. Prior work has shown increased nociceptive responses in adolescent or adult rats born of stressed dams. However, the age at which those changes first occur is not known. The aim of the present study was to evaluate the effect of prenatal stress on pain sensitivity in the formalin test in 7-day-old rats, behaviorally and by fos-like immunoreactivity (Fos-LI) in the lumbar spinal cord dorsal horn. The behavioral response to intraplantar injection of formalin is represented by two nociceptive phases separated by an interphase during which nociceptive responses decrease; the interphase is not seen until the start of the third postnatal week and appears as descending inhibitory monoaminergic systems develop. Prenatally stressed infants showed increased nociceptive responses in the second, tonic phase and a large increase in the number of formalin-induced Fos-LI neurons in the lumbar dorsal horn, a result consistent with the behavioral data. The increased nociception in prenatally stressed 7-day-old pups may be associated with the decrease in the intensity of serotonin-like immunoreactivity and density of serotonergic cells in the lumbar spinal cord dorsal horn and the dorsal raphe nucleus reported earlier.

Behavior ontogeny in the elevated plus-maze: prenatal stress effects

Prenatal stress is a putative model for studying some psychopathological disorders. Indeed, submitting pregnant animals to stress leads to enhanced anxiety in the adult offspring. However, little is known about how prenatal stress effects interacts with anxiety throughout development. To study this issue, prenatally stressed rats were tested in the elevated plus-maze at different ages. During pregnancy female rats were submitted to uncontrollable electric foot shock sessions every other day or kept undisturbed (controls). After delivery, litters from control and stressed dams were left undisturbed from the 3rd to the 14th postnatal days. Male and female rats were tested in the elevated plus-maze at the ages of 30, 45 or 60 days. The following measures were taken in the elevated plus-maze: number of entries and time spent in the arms (or their extremities) and frequency and time spent in naturalistic behaviors (stretching, rearing, end exploring, grooming and head dipping). Decreases in the percentage of entries into and in the time spent (only females) in the open arms were shown by 60-day-old prenatally stressed rats, but not by 30- and 45-day old. Increased open arm ends exploration was shown by 45-day-old prenatally stressed males. Rearing behavior was found to increase with age, a phenomenon more pronounced in females. Additionally, at the younger ages prenatally stressed rats were heavier than controls, an effect which disappeared at young adulthood. In conclusion, anxiogenic prenatal stress effects in the elevated plus-maze could only be detected at early adulthood, not before. Nonetheless, at late adolescence (45 days of age) prenatal stress leaded to an anxiolytic-like effect which can be interpreted as increased risk-taking behavior.

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.

Prenatal stress produces more behavioral alterations than maternal separation in the elevated plus-maze and in the elevated T-maze

Prenatal stress and maternal separation are used in a large number of studies on early adversity consequences and present some similarities in their effects. The present work investigates the behavioral effects of these two procedures on two models of anxiety: the elevated plus-maze and the elevated T-maze. During pregnancy, female rats were submitted to uncontrollable electric foot shock sessions every other day or kept undisturbed. After delivery, litters from undisturbed dams were submitted to either 180-min daily periods of maternal separations from the 3–14th postnatal days or maintained with the dams all the time. Litters from the stressed dams were left undisturbed from the 3–14th postnatal days. Only males were tested. In adulthood, rats were tested in the elevated T-maze or in the elevated plus-maze. In the latter procedure half the subjects were submitted to a 60-min period of restraint immediately before being tested. The following measures were taken in the elevated plus-maze: frequency and time spent in entries into the arms, stretching, rearing, grooming and head dipping. In the T-maze measures of avoidance and escape latencies were used. Our data indicated that prenatal stress had more pronounced anxiogenic effects than maternal separation, as judged by reduced exploration of the open arms of the elevated plus-maze, but mainly after the restraint stress, and increase in avoidance latencies in the elevated T-maze. The other measures not directly involved in the elevated plus-maze arm exploration yielded similar results. Our data indicate that prenatal stress causes more anxiogenic effects in adulthood than maternal separation but, in the elevated plus-maze, these anxiogenic effects are better seen immediately after an acute stress.

P38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction.

Stress is gaining increasing acceptance as an independent risk factor contributing to adverse cardiovascular outcomes. Potential mechanisms responsible for the deleterious effects of stress on the development and progression of cardiovascular disease remain to be elucidated. An established animal model of stress in humans is the prenatally stressed (PS) rat. We stressed rats in their third trimester of pregnancy by daily injections of saline and moving from cage to cage. Male offspring of these stressed dams (PS) and age-matched male control offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk of age. Echocardiography revealed a significant decrease in fractional shortening in PS + R vs. controls + R (45.8 +/- 3.9 vs. 61.9 +/- 2.4%, PS + R vs. controls + R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also revealed diminished fractional shortening (6.7 +/- 0.8 vs. 12.7 +/- 1.1%, PS + R vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to isoproterenol (P < 0.01; n = 24) determined by automated border detection. The p38 mitogen-activated protein (MAP) kinase inhibitor SB-203580 blocked p38 MAP kinase phosphorylation, reversed the depression in fractional shortening, and partially ameliorated the blunted adrenergic signaling seen in adult rat ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac myocytes by stress may be sufficient to lead to myocardial dysfunction in animal models and possibly humans.

Sexually dimorphic effects of prenatal stress on cognition, hormonal responses, and central neurotransmitters.

Exposure to stress during gestation results in physiological and behavioral alterations that persist into adulthood. This study examined the effects of prenatal stress on the postnatal expression of sexually differentiated cognitive, hormonal, and neurochemical profiles in male and female rats. Pregnant dams were subjected to restraint stress three times daily for 45 min during d 14-21 of pregnancy. The offspring of control and prenatally stressed dams were tested for anxiety-related and cognitive behaviors, stress and gonadal steroid hormone levels, as well as monoamines and metabolite levels in selected brain regions. Postnatal testosterone levels (measured at 1 and 5 d) did not differ between controls and prenatally stressed animals. In adulthood, the serum corticosterone response to stress was attenuated in prenatally stressed females, eliminating the sex difference normally observed in this parameter. Prenatally stressed females exhibited higher anxiety levels, evidenced by longer open field entry latencies. Prenatal stress had no effect on object recognition memory, but eliminated the advantage normally seen in the male performance of a spatial memory task. Neurochemical profiles of prenatally stressed females were altered toward the masculine phenotype in the prefrontal cortex, amygdala, and hippocampus. Thus, prenatal stress altered subsequent cognitive, endocrine, and neurochemical responses in a sex-specific manner. These data reinforce the view that prenatal stress affects multiple aspects of brain development, interfering with the expression of normal behavioral, neuroendocrine, and neurochemical sex differences. These data have implications for the effects of prenatal stress on the development of sexually dimorphic endocrine and neurological disorders.

Rabbits behaviour under modern commercial production conditions – a review

Abstract. Recently, much work has been done to record the diurnal peak of does receptivity. It was found that the highest was in the morning and before allowing suckling. Such studies suggested that mating should be achieved in the morning or before suckling to avoid the negative effect of the circadian peak of prolactin on receptivity that occur around 15.00 to 19.00 h and after each suckling. Some cases of pseudo-pregnancy might be prevented by double mating; the second mating should be within at most five hours after the first, since mating later than this would have no effect. Total parturition time would be 10–14 minutes for a large litter and 5–7 minutes for an average litter, although parturition could be induced to allow prompt attention to does with poor maternal instinct and to those kindle for the first time kindling and to avoid situations such as: kindling at night or in cold weather and/or to avoid the variability in gestation periods (29 to 34 days). Mother-litter separation during night can influence species specific nursing behaviour and may lead to lower weaning weights of pups. Applying good management programs, as well as, change of place, gentle handling of the stressed dams, correcting nutritional deficiencies and inadequate drinking water and provision of adequate amount of straw, may well eliminate stress, correct behavioural disorders and certain types of maternal anomalies which appear to be not under the control of hormonal or genetic factors. Welfare for caged rabbits can be improved by feeding the animals in the afternoon rather than in the morning. Aggressive behaviour was greater in rabbits on nipple drinkers than in those on troughs. In conclusion, better understanding of rabbits natural behaviour under the different conditions, maintains optimal production compatible with welfare demands. Below, description of rabbits behaviour and its relation with modern commercial production conditions, were discussed.

Effects of prenatal stress on maternal behavior in the rat

Some authors reported a link between maternal stress and disturbances in their infants. Because of difficulties due to human research, the effects of prenatal stress have to be examined in animal models. Our approach was original in that the stressor was an ecological one and was applied at a given gestational day. Indeed, the stressor was a cat and the effects of stress on maternal behavior were investigated in five groups of 10 female rats: two groups were composed of females which were acutely stressed either at the 10th or the 14th gestational day; two other groups were composed of females which were repeatedly stressed either at the 10th or the 14th gestational day; the fifth group comprised non-stressed females. Plasma corticosterone concentrations measured in blood samples collected from dams just after stress were significantly higher than in controls showing that cat represents an efficient stressor for rats. Maternal behavior was recorded during 30 min at the 2nd, 4th, and 6th postnatal days. In all cases, stressed dams’ activities directly directed towards the pups (retrieving, sniffing and licking), those non-directly directed towards the pups (carrying its tail and digging the sawdust), and those directed towards themselves (eating, drinking and resting) were altered to different degrees. These alterations in maternal behavior can explain, at least in part, the mortality and the low growth rate observed in pups born from stressed dams.

Handling during Pregnancy in the Blue Fox (Alopex lagopus): The Influence on the Fetal Pituitary–Adrenal Axis

Previous studies revealed that handling is a stressor for farmed blue foxes. The present study was designed to examine the effects of a 1-min daily handling stress applied to pregnant blue fox vixens on the function of the fetal pituitary–adrenal system. Plasma concentrations of adrenocorticotropin hormone (ACTH), cortisol, and progesterone, adrenal content of cortisol and progesterone, in vitro adrenal production of these steroids and response to ACTH, and adrenal weights were measured in control (C; n = 73) and stressed (S; n = 58) fetuses. The ACTH levels were lower in stressed fetuses than in the controls (C: males, 128.6 ± 6.1 pg/ml; females, 165.9 ± 6.1 pg/ml; S: males, 122.3 ± 5.4 pg/ml; females, 145.0 ± 8.1 pg/ml; P < 0.05). In contrast, increased plasma cortisol concentrations in both sexes were demonstrated in stressed compared with control fetuses (C: males, 9.2 ± 0.4 ng/ml; females, 9.2 ± 0.4 ng/ml; S: males, 11.8 ± 0.7 ng/ml; females, 13.2 ± 0.7 ng/ml; P < 0.00001). The same difference was observed in plasma progesterone concentrations (C: males, 1.54 ± 0.07 ng/ml; females, 1.49 ± 0.10 ng/ml; S: males, 1.86 ± 0.11 ng/ml; females, 1.74 ± 0.10 ng/ml; P < 0.01). Prenatal stress did not change the baseline adrenal production of cortisol but prevented the cortisol response to ACTH in female fetuses and decreased the progesterone production in both sexes. Additionally, prenatally stressed fetuses of both sexes had significantly lower adrenal weights than controls (C: males, 9.4 ± 0.3 mg; females, 9.5 ± 0.4 mg; S: males, 8.1 ± 0.3 mg; females, 8.2 ± 0.4 mg; P < 0.001). These results indicate that prenatal handling stress induces a dysregulation of the pituitary–adrenal axis in the fetus and suggest that increased plasma glucocorticoids in the stressed dam can cross the placenta and influence the fetal hypothalamic–pituitary–adrenal axis.

Effects of stress during pregnancy on maternal behavior in mice

The effects of stress experienced during pregnancy and raising stressed offspring on maternal behavior were investigated in Swiss–Webster mice. Dams were either stressed or not stressed during pregnancy, and raised either prenatally stressed or nonstressed cross-fostered pups. Maternal behaviors such as grooming, nursing, pup retrieval and maternal aggression were assessed during the first 4 days after birth. Nonstressed dams raising stressed pups and stressed dams raising nonstressed pups groomed and nursed their pups significantly less than did control dams (stressed dams raising stressed pups and nonstressed dams raising nonstressed pups). Nonstressed dams raising stressed pups were also the slowest to retrieve both the first and last pup in retrieval tests. Nonstressed dams raising nonstressed pups were significantly less aggressive than other dams. In contrast, stressed dams raising stressed pups exhibited high levels of nursing and grooming, retrieved their pups rapidly and were very aggressive towards an intruder. These results indicate that raising stressed pups, or experiencing stress during a pregnancy can have significant effects on maternal behaviors. Stressed dams raising stressed pups exhibit maternal care comparable to that of nonstressed dams raising nonstressed pups at least for nesting/nurturing behaviors, and show increased levels of aggression and pup retrieval.

Brain N-acetyl aspartate concentrations measured by 1H MRS are reduced in adult male rats subjected to perinatal stress: preliminary observations and hypothetical implications for neurodevelopmental disorders

The present study was undertaken to determine if the concentration of brain N-acetyl-aspartate (NAA), a putative neuronal marker, is reduced in adult rats subjected to stress during the perinatal period. As the prenatal stressor, pregnant rats were subjected to restraint stress for one hour twice daily from days 14–21 of gestation; stressed offspring were reared by normal dams and studied as adults. As the postnatal stressor, normal pups were reared by prenatally stressed dams and studied as adults. As compared to non-stressed controls ( n=6), NAA concentrations were significantly reduced 21 and 25% in left frontal cortex from the prenatal ( n=4) and postnatal ( n=6) stress groups, respectively. The data suggest that in perinatally stressed adult offspring permanent neuronal damage or loss has occurred. While no direct causal associations between perinatal stress and the developmental of particular disorders can be inferred from these limited data, the effects of perinatal stress on subsequent brain neuropathology are reviewed, particularly in relation to NAA. For hypothesis-generating purposes, the possible relevance of stress and NAA to the neurodevelopmental hypothesis of schizophrenia is discussed in greater detail.

Prolonged stress-induced elevation in plasma corticosterone during pregnancy in the rat: implications for prenatal stress studies.

Experiments were conducted to test the hypothesis that exposure to uncontrollable stress during pregnancy results in a heightened elevation of plasma glucocorticoids. Rats were exposed to uncontrollable electric tail shocks every other day during the 3 weeks of pregnancy. Plasma corticosterone concentrations in stressed dams increased significantly from gestation days 4 to 20. Importantly, this increase in plasma corticosterone occurred 24- and 48-h after exposure to stress suggesting a prolonged elevation in stress-induced glucocorticoid secretion. In addition, the stress-induced rise in plasma corticosterone was accompanied by a significant decrease in maternal levels of corticosteroid binding globulin which suggests increased circulating levels of free corticosterone. Significant stress-induced elevations in plasma corticosterone also occurred in fetuses that were examined on gestation day 20. Furthermore, a significant positive correlation was found between maternal and fetal plasma corticosterone. Results demonstrate that repeated exposure to uncontrollable stress increases plasma concentrations of glucocorticoids throughout pregnancy. In the unbound state, corticosterone may be highly effective in producing alterations in brain development of offspring. These data have important implications for understanding the process underlying the effects of prenatal stress.

Effect of Prenatal Stress on Opioid Component of Exploration in Different Experimental Situations

Prenatal stress interferes with the expression of opioid systems in rats. The present study determined the effect of prenatal stress on the opioid-influenced component of exploratory behavior, defined as the difference between the behavior of vehicle-treated and naloxone-treated rats, in three novel situations previously shown to cause different degrees of arousal. Pregnant rats were stressed three times weekly on a random basis by noise and flashing lights. Experiments were performed on 60–70-day-old offspring (male and female) of control and stressed dams. Fifteen minutes after injection of vehicle or naloxone (1 mg/kg), the proportion of time spent in eight different behavioral parameters, including locomotion, rearing, sniffing, hole poking, pivoting, and grooming, was assessed during 4 min of exposure to an open field, either with or without prior exposure to a hole box. The magnitude of the depressant effect of naloxone on exploration depended on the nature of the environment, previous experience of the animal in another situation, and the parameter of exploration assessed. The opioid-influenced component of locomotion and rearing was significantly reduced by prenatal stress, particularly in female rats. Further studies using a cross-fostering design are needed to assess the relative contributions of pre- and postnatal factors to the reduction of opioid activity in prenatally stressed rats. More specific opioid antagonists could be used to determine the nature of the opioid receptors involved.