Effects of Chronic Prenatal Restraint Stress on Anxiety in Post Weaned Male and Female Wistar Rats (original) (raw)
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Journal of Neurology and Neuroscience
Background: Several studies focus on the effects of prenatal stress in adulthood. Relatively little is known about the early neurodevelopmental consequences of such experiences and their predictive value. Thus we examined the early neurobehavioral responses of offspring whose mothers were exposed to restraint stress. Methods and results: Pregnant rats were exposed to 60 minutes restraint stress twice a day for seven days in different periods of pregnancy (early/mid and late phase). After birth, offspring were examined for the maturation of neural signs and reflexes daily for 3 weeks. Mid-pregnancy stress resulted in a subtle faster development in the appearance of eyelid and auditory startle reflexes, and in the disappearance of crossed extensor reflex. Pups exposed to stress in the last week of intrauterine life displayed a delay in air righting and showed a slight enhancement in the appearance of auditory startle. Conclusion: Based on our present findings, the deleterious consequences of prenatal stress are not apparent during the early developmental stages at least not detectable with the battery of test most widely used to examine neurobehavioral development. However, these findings draw the attention of the need of careful awareness in later ages in spite of the normal neurobehavioral development of newborns exposed to prenatal stress.
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.
Stress, 2019
Prenatal stressful events have long-lasting consequences on behavioral responses of offspring. While the effects of gestational and maternal stress have been extensively studied on psychological alterations in the progeny, little is known about effects of each parent's pre-conception life events on emotional responses in offspring. Here, the effect of maternal and/or paternal pre-conception stress was investigated on anxiogenic responses of offspring. Male and female adult rats were subjected to predatory stress (contactless exposure to a cat for 1 þ 1 h per day) for 50 (male, n: 12) and 15 (female, n: 24) consecutive days; controls were not exposed. After the stress procedure, the control and stressed rats were mated to create four types of breeding pairs: control female/control male, stressed female/control male, control female/stressed male, and stressed female/stressed male. On postnatal days 30-31, the offspring were tested on the elevated plus maze and plasma corticosterone concentration was measured. Half of the pups were exposed to acute predatory stress before the elevated plus maze test. In most subgroups, corticosterone and anxiety-like behaviors in the offspring with both or only one parent exposed to pre-gestational stress increased compared to their control counterparts. However, under acute stress conditions, a different sex-dependent pattern of anxiety responses emerged. The combined effects of maternal and paternal stress were not additive. Hence, individual offspring behaviors can be influenced by the former life stress experiences of either parent. Incorporation of genetic and epigenetic aspects in development of neurobehavioral abnormalities and reprograming of the hypothalamicpituitary-adrenal axis may contribute to this phenomenon. LAY SUMMARY Early life stress (including during pregnancy) is known to have long-lasting effects on offspring, including emotional behaviors. Whether individual anxiety behaviors can be influenced by stress experiences of each parent even before a pregnancy is less well-understood. Our findings from this study on rats exposed to predator stress before mating suggest that maternal or paternal adult life events prior to pregnancy can lead to maladaptive behavior in their offspring later in life.
Journal of Behavioral and Brain Science, 2015
There has been an increasing importance of studies that link sex to stress coping processes. Recently, we reported that male and female Wistar rats responded differently to prenatal stress (PS) under basal conditions. The aim of the present study was to determine the influence of sex on behaviour and coping strategies, as an effect of gestational adversity in rats that were exposed to an uncontrollable stressor. Once the animals reached adulthood, the offspring from stressed/nonstressed dams were subjected or not to antidepressant treatment with Sertraline. After that, they were exposed to a single inescapable shock (IS) session, in which the rats were further tested for escape behaviour along 10 days, as a model of learned helplessness (LH). In prenatally stressed animals after the IS, behavioural differences appeared in a sex specific manner. Males proved to be more susceptible to the adverse context than females, exhibiting behavioural despair in a large percentage of the cases. Surprisingly, PS did not affect shock escape failure, but did affect learning performance in a sex dependent manner. In females, PS led them to learn to avoid shocks, learning better than controls, and by contrast, PS males did not learn to avoid shocks and displayed some signs of anhedonia. Sertraline did not help animals to avoid shocks, but helped them to escape from it. Our data indicate the existence of sex dependent behavioural differences in PS animals when facing an uncontrollable stress situation, in which the changes induced by PS were not only different, but opposite between sexes.
2018
The foetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behaviour. The present study aimed to determine the physiological and behavioural effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 to 21, a critical period for foetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety-and depressive-like behaviours, as well as spontaneous social interaction. We also assessed maternal behaviours and 2 stress markers: basal vs acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behaviour, whereas both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation, as well as anxiety-and depressive-like behaviours, were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on hypothalamic-pituitary- adrenal (HPA) axis activity and on behaviour during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, and they were also more anxious and experienced depressive-like behaviours. These results are useful with respect to studying the neurobiological basis of childhood depression at a preclinical level.
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.
PLOS ONE, 2017
Background Stress is an inevitable part of life, and maternal stress during the gestational period has dramatic effects in the early programming of the physiology and behavior of offspring. The developmental period is crucial for the well-being of the offspring. Prenatal stress influences the developmental outcomes of the fetus, in part because the developing brain is particularly vulnerable to stress. The etiology of birth defects of the offspring is reported to be 30-40% genetic and 7-10% multifactorial, with the remaining 50% still unknown and also there is no clear cause for neonatal mortality and still-birth. Objective The present study explores the association of maternal psychological stress on mother and the offspring's incidence of birth defects, stillbirth, and neonatal mortality. Study design Pregnant animals were restrained to induce psychological stress (3 times per day, 45 minutes per session). Except control group, other animals were exposed to restraint stress during the gestational period: early gestational stress (EGS, stress exposure during 1 st day to 10 th days of gestational period), late gestational stress (LGS, stress exposure during 11 th day to till parturition), and full term gestational stress (FGS, stress exposure to the whole gestational period). The effects of maternal stress on the mother and their offspring were analyzed. Results Expectant female rats exposed to stress by physical restraint showed decreased body weight gain, food intake, and fecal pellet levels. Specifically, the offspring of female rats subjected to late gestational and full term gestational restraint stress showed more deleterious effects, such as physical impairment (LGS 24.44%, FGS 10%), neonatal mortality
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.
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.