Effects of Maternal Stress during Different Periods of Pregnancy on the Early Neurobehavioral Response of Rats (original) (raw)
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Effects of Chronic Prenatal Restraint Stress on Anxiety in Post Weaned Male and Female Wistar Rats
Cherian et al. Summary Stress in adulthood can have a profound effect on physiology and behavior, but the extent to which prolonged maternal stress affect brain function of offspring when they are adult remains primarily unknown. Controversies exist in literature regarding sexual dimorphism in the effects of prenatal stress on the postnatal cognitive behavioral development. To investigate the effect of prenatal stress on locomotor, exploratory and emotional development, pregnant rats of Wistar strain were subjected to restraint stress from E11 till delivery. Male and female pups born to these stressed rats were subjected to open field test on 21 st day of postnatal life. Results were compared with rats of the same age and sex born to control mothers, which were not stressed. The results showed that prenatal maternal restraint stress affected both male and female offsprings during young age. These results suggests that prolonged maternal stress leads to long lasting malfunction of th...
Neurodevelopment milestone abnormalities in rats exposed to stress in early life
Neuroscience, 2007
Manipulation of the corticosteroid milieu by interfering with the mother-newborn relationship has received much attention because of its potential bearing on psychopathology later in life. In the present study, infant rats that were deprived of maternal contact between the 2nd and the 15th postnatal days (MS 2-15 ) for 6 h/day were subjected to a systematic assessment of neurodevelopmental milestones between postnatal days 2 and 21. The analyses included measurements of physical growth and maturation and evaluation of neurological reflexes. Although some somatic milestones (e.g. eye opening) were anticipated, MS 2-15 animals showed retardation in the acquisition of postural reflex, air righting and surface righting reflexes, and in the wire suspension test; the latter two abnormalities were only found in males. A gender effect was also observed in negative geotaxis, with retardation being observed in females but not males. To better understand the delay of neurological maturation in MS 2-15 rats, we determined the levels of various monoamines in different regions of the brain stem, including the vestibular area, the substantia nigra, ventral tegmental area and dorsal raphe nuclei. In the vestibular region of MS 2-15 rats the levels of 5-HT were reduced, while 5-HT turnover was increased. There was also a significant increase of the 5-HT turnover in MS 2-15 animals in the raphe nuclei, mainly due to increased 5-hydroxyindoleacetic acid (5-HIAA) levels, and an increase of 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the ventral tegmental area (VTA) of stressed females. No significant differences were found in the immunohistochemical sections for tyrosine and tryptophan hydroxylase in these regions of the brain stem. In conclusion, the present results show that postnatal stress induces signs of neurological pathology that may contribute to the genesis of behavioral abnormalities later in life. (N. Sousa). Abbreviations: DOPAC, 3,4-dihydroxyphenylacetic acid; HPA, hypothalamic-pituitary-adrenal; HPLC/EC, high performance liquid chromatography, combined with electrochemical detection; HVA, homovanillic acid; MS 2-15 , maternal separation between the 2nd and the 15th postnatal days; PND, postnatal day; SHRP, stress hypo-responsive period; SN, substantia nigra; TH, tyrosine hydroxylase; VTA, ventral tegmental area; 5-HIAA, 5-hydroxyindoleacetic acid.
Effects of prenatal stress on maternal behavior in the rat
Developmental Brain Research, 2002
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.
Gestational chronic mild stress: Effects on acoustic startle in male offspring of rats
2011
An increasing number of scientific studies indicate that maternal stress during pregnancy influences fetal development of the nervous system and thereby the behavioural phenotype. We have previously reported attenuated prepulse inhibition (PPI) of the startle reaction in adult female rats derived from dams exposed to chronic mild stress (CMS) during gestation. In humans, decreased PPI has been reported to be associated with anxiety. Because of its potential translational value across species, the modulation of startle reactivity may be a useful tool in examining altered emotional reactivity following prenatal insults. The present study aimed at investigating whether prenatally stressed male offspring would display altered startle phenotype. Stress was induced by maternal gestational exposure to alternating procedures, i.e. CMS. At the age of 3 months, half of the offspring were blood sampled under restraint. At the age of 6 months, i.e. three months later, all animals were tested in the acoustic startle and the light enhanced startle (LES) paradigm. Control and CMS male offspring showed similar basal startle and LES levels. Maternal gestational exposure to the relatively mild, variable paradigm of stressors affected the PPI response pattern in male rats. In prenatally manipulated males, the PPI response differed statistically significantly, depending on prior exposure to an episode of postnatal acute stress (blood sampling under restraint). In contrast, the PPI response in control males was unaffected by this postnatal experience. The present work supports the hypothesis that the maternal environment is a long-term determinant of phenotypic differences in sensitivity to stressors.
Prenatal and adult stress interplay — behavioral implications
Brain Research, 2010
The origin of adult behavior and the possible pathogenesis of psychiatric disorders remain elusive, but extensive research indicates that interaction of genes and environment play a crucial role for adult phenotype. Differences in susceptibility may arise by earlier experiences and genomic variables, either alone or in combination. The acoustic startle response (ASR) has been shown to be altered in patients with several psychiatric diseases, a change that could result from a persistent sensitization caused by chronic arousal secondary to a traumatic incident. The current work hypothesized that a single aversive procedure would induce long-term hyperactivity in the HPA-axis of rats that had become vulnerable by prenatal stress, and thereby change reactivity in the ASR. Prenatal stress was achieved by maternal gestational exposure to Chronic Mild Stress (CMS). At age 3 months, the offspring were blood sampled by a stressful procedure, and subsequently tested in the acoustic startle paradigm. Prenatal CMS strongly reduced prepulse inhibition (PPI) whereas postnatal blood sampling under restraint generally increased PPI. Our data demonstrate interplay between pre-and postnatal stressful events, but also that this interaction is complex and could influence the interplay between PPI and basal startle. Our results suggest that circumstances dating back to early development may have implications for adult life behavior, and based on this we propose a new theory of a threshold in the induction of a stress response in the ASR test, which influences whether the PPI or basal startle response will be affected.
Effects of prenatal stress on developmental anatomy of the brain and adult behavioural pathology
Anatomy (International Journal of Experimental and Clinical Anatomy), 2009
During critical or sensitive periods of development, the brain is highly plastic and particularly vulnerable to environmental adverse effects, including stress. In response to gestational stress, activation of the sympathetic system, the HPA axis and the central limbic stress loop increase the level of circulating glucocorticoids and catecholamines in both mother and foetus. Exposure to the excess amount of corticosteroids permanently reduces the glucocorticoid and mineralocorticoid receptors; thereby leading to an attenuation of the HPA axis feedback sensitivity and enhanced responsiveness to stress in the adult offspring. In the assessment of consequences at the behavioural, functional, and morphological levels; experimental animal models of maternal stress are extremely useful, in which the timing, intensity and duration of stress exposure can be readily controlled. These animal studies have revealed important links between prenatal stress exposure, lifelong changes in the HPA function, and enhanced risk for subsequent psychopathology in a sex-specific manner. The aim of this review is to examine the impacts of prenatal stress on developmental anatomy of the brain, particularly focusing on the relevant emotional and behavioural outcomes within the context of current data obtained from experimental animals.
Teratology, 1978
Rats were subjected to restraint stress for nine hours daily, on three consecutive days, a t various stages of pregnancy from days 9-20, and the postnatal development and behaviour of the offspring assessed on a wide-ranging battery of tests. Stress a t any of the stages of pregnancy investigated caused a significant decrease in offspring body weight persisting up to 6 weeks of age, and delayed the appearance of certain developmental landmarks such as ear opening, auditory startle and cliff avoidance responses. Postnatal mortality and impairment of ability to orient to the home cage were also significantly increased in the offspring from rats stressed on days 18-20 of pregnancy. In a second experiment, the effects of restraint stress on days 18-20 were investigated in more detail. At birth, stressed and control offspring were fostered onto mothers from the same treatment group or cross-fostered onto mothers from the opposite treatment group and assessed as before, to determine whether the adverse effects observed in the first experiment were prenatally or postnatally mediated. The effects were most marked in prenatally stressed pups reared by stressed mothers and least marked in controls reared by controls, with the other two cross-fostered groups being intermediate; this indicates that the effects were induced partly prenatally a t the time of treatment and partly postnatally by the rearing mothers that had been stressed.
Stress during gestation induces lasting effects on emotional reactivity of the dam rat
Behavioural Brain Research, 2004
Human and animal studies indicate that repeated stress during pregnancy can produce long-term biological and behavioural disorders in the offspring. In contrast, although maternal stress is supposed to induce an increase of maternal anxiety, few studies have been conducted to demonstrate it. Therefore, in the present study we examined the emotional reactivity in stressed (chronic restraint stress applied 3× 45 min per day during the last week of pregnancy) and unstressed females rats after the weaning of their pups. Restraint stress procedure reduced the body weight gain both during pregnancy and up to four weeks after the stress period. Stressed dams presented a reduction of exploration and of corticosterone levels when exposed to a novel environment (25 and 49 days post-stress). They spent less time in the open arms of the elevated plus-maze (26 days post-stress). Finally, they showed no increase in the time spent in immobility after a second exposure to the forced-swim test (35-36 days post-stress). In the contrary, such differences were not observed when the chronic stress procedure was applied on virgin females. Overall, our results show that, chronic stress during gestation induces lasting effects on emotional reactivity of the dams, thus indicating that gestation constitutes a critical period in the vulnerability to stressful events also for the mother.
Brazilian Journal of Medical and Biological Research, 1999
Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS) during pregnancy (prenatal stress; PS group). Control pregnant rats (C group) were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36) while the other PS pups were cross-fostered with C dams (PSF group, N = 47) and the other C pups were cross-fostered with PS dams (CF group, N = 58). Pups were undisturbed until weaning (postnatal day 28). The male offspring underwent motor activity tests (day 28), enriched environment tests (day 37) and social interaction tests (day 42) in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncans test, P<0.05). The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; c 2 test, P<0.05) and lower body weight than controls at days 28 and 60 (Duncans test, P<0.05 and P<0.01, respectively). The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncans test, P<0.01 for PS group and P<0.05 for CF and PSF groups). In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncans test, P<0.05). Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncans test, P<0.05). In fact, CVS treatment during gestation plus suckling with a previously stressed mother caused long-lasting physical and behavioral changes in rats. Cross-fostering PS-exposed pups to a dam which was not submitted to stress counteracted most of the harmful effects of the treatment. It is probable that prenatal stress plus suckling from a previously stressed mother can induce long-lasting changes in the neurotransmitter systems involved in emotional regulation. Further experiments using neurochemical and pharmacological approaches would be interesting in this model.
PLoS ONE, 2008
Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS (''PRS rats'') showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sexdependent and that the behavioral outcome may diverge in males and females.