Prenatal and adult stress interplay — behavioral implications (original) (raw)
Related papers
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.
Neuroscience, 2011
Stress is a risk factor for the development of affective disorders, including depression, post-traumatic stress disorder, and other anxiety disorders. However, not all individuals who experience either chronic stress or traumatic acute stress develop such disorders. Thus, other factors must confer a vulnerability to stress, and exposure to early-life stress may be one such factor. In this study we examined prenatal stress (PNS) as a potential vulnerability factor that may produce stable changes in central stress response systems and susceptibility to develop fear- and anxiety-like behaviors after adult stress exposure. Pregnant Sprague-Dawley rats were immobilized for 1 h daily during the last week of pregnancy. Controls were unstressed. The male offspring were then studied as adults. As adults, PNS or control rats were first tested for shock-probe defensive burying behavior, then half from each group were exposed to a combined chronic plus acute prolonged stress (CAPS) treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/d, 14 days) followed on day 15 by a single session of sequential acute stressors (social defeat, immobilization, cold swim). After CAPS or control treatment, different groups were tested for open field exploration, social interaction, or cued fear conditioning and extinction. Rats were sacrificed at least 5 days after behavioral testing for measurement of tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) expression in specific brain regions, and plasma adrenocorticotropic hormone (ACTH) and corticosterone. Shock-probe burying, open field exploration and social interaction were unaffected by any treatment. However, PNS elevated basal corticosterone, decreased GR protein levels in hippocampus and prefrontal cortex, and decreased TH mRNA expression in noradrenergic neurons in the dorsal pons. Further, rats exposed to PNS plus CAPS showed attenuated extinction of cue-conditioned fear. These results suggest that PNS induces vulnerability to subsequent adult stress, resulting in an enhanced fear-like behavioral profile, and dysregulation of brain noradrenergic and hypothalamic-pituitary-adrenal axis (HPA) activity.
Cerebral Cortex, 2019
The prepulse inhibition (PPI) of the acoustic startle reflex (ASR), as an index of sensorimotor gating, is one of the most extensively used paradigms in the field of neuropsychiatric disorders. Few studies have examined how prenatal stress (PS) regulates the sensorimotor gating during the lifespan and how PS modifies the development of amyloid-beta (Aβ) pathology in brain areas underlying the PPI formation. We followed alternations in corticosterone levels, learning and memory, and the PPI of the ASR measures in APPNL-G-F/NL-G-F offspring of dams exposed to gestational noise stress. In-depth quantifications of the Aβ plaque accumulation were also performed at 6 months. The results indicated an age-dependent deterioration of sensorimotor gating, long-lasting PS-induced abnormalities in PPI magnitudes, as well as deficits in spatial memory. The PS also resulted in a higher Aβ aggregation predominantly in brain areas associated with the PPI modulation network. The findings suggest the ...
Psychopharmacology, 2011
Rationale Early life stress is a risk factor for the development of psychopathology in later life. Consequences of adverse life events, however, may depend on the genetic makeup of an individual. Reduced serotonin 1A receptor function may predispose to the development of anxiety disorders. Objective Determine susceptibility of serotonin 1A receptor knockout (1AKO) mice on different background strains to the effects of maternal separation (MS) by assessing startle plasticity in adulthood. Methods 1AKO mice on a 129S6 and a Swiss Webster (SW) background were used. MS groups were separated daily from their mother for 180 min/day from postnatal days 2 to 14. Control groups underwent normal animal facility rearing. In adulthood, effects on acoustic startle response, habituation, prepulse inhibition (PPI), and foot shock sensitization were determined. Results MS increased startle reactivity and reduced PPI in 129S6 mice. These effects of MS were independent of genotype. MS had no effect on the other readouts. In SW mice, MS had no consistent effect on startle reactivity and did not alter startle plasticity in wild type or in 1AKO mice. 1AKO mice did not differ from wild-type mice in startle plasticity. Conclusion Serotonin 1A receptor deletion does not enhance vulnerability to the effects of MS on startle plasticity. The life-long increase in startle reactivity and PPI deficit induced by MS are strain-dependent. Further, the use of startle reactivity and plasticity may have added value in translational studies relating to early life stress.
Early emergence of increased fearful behavior in prenatally stressed rats
Physiology & Behavior, 2005
We have been studying the mildly prenatally stressed (PS) rat as a potentially useful animal model of anxiety disorders. Previously we have demonstrated that there are anatomical and biochemical alterations in the amygdalas of adult PS offspring and that these offspring show increased fearful behaviors. However, human data indicate that anxiety disorders often present first in early childhood and then persist throughout adolescence and adulthood. To determine if PS rats also model this characteristic of human anxiety disorders, here we asked whether behavioral indices of increased fear would be detectable at an early age. We tested the hypotheses that young PS rats would show increased behavioral fearfulness in response to an acute stressor and that this would increase with age. A mild prenatal stressor, consisting of removal of the dam from the home cage and administration of a subcutaneous injection of 0.1 ml of 0.9% saline daily, was administered during the last week of pregnancy. Offspring were tested in the defensive-withdrawal apparatus before and after exposure to restraint stress at 25, 45 and 60 days of age. PS animals showed increased defensive-withdrawal behavior following the stressor and were more fearful following restraint when compared to controls (CON). This was significant at P45 and increased to P60. Hence, fearful behaviors in PS rats emerge prior to sexual maturation and increase in magnitude thereafter, further validating our model as a means to investigate the underpinnings of anxiety disorders.
The effects of an early stressful life event on sensorimotor gating in adult rats
Schizophrenia Research, 1998
Thc,e is increasing evidence that patients suffering from schizophrenia have disturbances in the brain and other parts of the body indicative of a disturbed development. These findings have led to the so-called neurodevelopmental hypotheses of schizophrenia, which state that schizophrenia (or a predisposition lk)r this disease) resuhs from perinatal disturbances which affect the normal development of the central nervous system. In order to study such a possible relationship we have used early short-lasting (24 h) maternal deprivation, and studied the influence of this life event on prepulse inhibition of the acoustic startle at adult age in rats, since it has been shown that schizophrenic patients show a disruption of prepulse inhibition. The results show that early maternal deprivation significantly reduced prepulse inhibition when the animals were tested at postnatal day (pndt 69 t birth being pnd Iit. The effects were qualitatively similar when deprivation took place on pnd 3.6 or 9, ahhough at the later days the efl'ects were stronger. There was little influence on baseline startle response (except for a small reduction seen after depriwttion on pnd 6). In separate experiments it was shown that the effect of maternal deprivation on prepulse inhibition was not seen bel\~re puberty and was similar t\~r male and female offspring. Moreover, the effects could be reversed by' treatlnent with the chtssical antipsychotic, haloperidol, or the putative atypical antipsychotic, quetiapine (both given 15 mm bel\~re the prepulse inhibition experiment ). In summary, the results show that an early stressful life event can have a delayed influence on prepulse inhibition in rats, qualitatively similar to the disturbances seen m schizoph,enic patients. These data suggest that maternal deprivation {i.e.. a 24 h separation of rat pups from their mother early in life) may represent an interesting animal model l\~r investigating the influence of early life events on the inl\~rmation processing and general functioning of an individual at aduh age. ,c: 1998 Elsevier Science B.V.
Maternal social stress modulates the development of prepulse inhibition of startle in infants
Developmental cognitive neuroscience, 2013
Stress during rearing has negative effects on the maturation of information processing in rodent offspring, but similar evidence in humans is absent. Prepulse inhibition (PPI) of startle is a measure reflecting the integrity of information processing. PPI does not depend on active cooperation, making it a suitable measure for studying newborns and infants. This study investigated whether postnatal development of infant PPI is influenced by self-reported stress in the mother. 49 healthy term-born infants were studied twice, four days after birth and again at four months. PPI was assessed by presentation of acoustic startle stimuli (95dB) either alone or preceded (SOA 120ms) by a prepulse (75dB). Mother's social stress levels were assessed with the modified Trier Inventory for the Assessment of Chronic Stress (TICS). Cortisol saliva samples were collected from mothers and their children. ANOVA revealed a different development of PPI in infants whose mothers reported enhanced stres...
Psychoneuroendocrinology, 2008
Exposure to stress during prenatal or early postnatal life can dramatically impact adult behavior and neuroendocrine function. We recently began to selectively breed Sprague-Dawley rats for high (high responder, HR) and low (low responder, LR) novelty-seeking behavior, a trait that predicts a variety of differences in emotional reactivity, including differences in neuroendocrine stress response, fear- and anxiety-like behavior, aggression, and propensity to self-administer drugs of abuse. We evaluated genetic–early environment interactions by exposing HR- and LR-bred animals to prenatal stress (PS) from pregnancy day 3–20, hypothesizing that PS exposure would differentially impact HR versus LR behavior and neuroendocrine reactivity. We evaluated novelty-induced locomotion, anxiety-like behavior, and corticosterone stress response in weanling (25-day-old) and adult HR–LR stressed and control males. Exposure to PS did not alter HR–LR differences in locomotion, but did impact anxiety-like behavior, specifically in LR animals. Surprisingly, LR animals exposed to PS exhibited less anxiety than LR controls. HR rats were not affected by PS, with both stress and control groups showing low levels of anxiety. PS differentially impacted neuroendocrine stress reactivity in young versus adult HR–LR animals, leading to an exaggerated corticosterone response in LR pups compared to LR controls, while HRs pups were unaffected. In contrast, exposure to PS produced an exaggerated stress response in HR adults, compared to HR controls, while LR animals were not significantly affected. These findings highlight how genetic predisposition may shape individual's response to early life stressors, and furthermore, show that a history of early life stress may differentially impact an organism at different points in life. Future work will explore neural mechanisms which underlie the different behavioral and neuroendocrine consequences of PS in HR versus LR animals.
Genes, Brain and Behavior, 2006
A growing body of research implicates genetic factors and childhood trauma in the etiology of neuropsychiatric diseases such as schizophrenia. However, there remains little understanding of how genetic variation influences early life stress to affect later disease susceptibility. Studies in rats have shown that postnatal maternal separation (MS) results in later deficits in prepulse inhibition of the acoustic startle response (PPI), an impairment in sensorimotor gating found in schizophrenic patients. In the present study, genetic differences in the effects of repeated MS on PPI were examined in eight inbred strains of mice (129S1/SvImJ, 129P3/J, A/ J, BALB/cJ, BALB/cByJ C57BL/6J, DBA/2J and FVB/NJ). Mice were assigned to either MS (180 min/day on postnatal days P0-P13), 'handling' (15 min/day, P0-P13) or facility-reared conditions and tested for PPI at 12 weeks of age. Results demonstrated major strain differences in the production of viable offspring irrespective of MS, leading to the exclusion of 129P3/J, A/J and BALB/cJ from the study. Pups from the five remaining strains exhibited marked differences in the acoustic startle response and PPI, confirming previous strain comparisons. However, MS produced no significant effects on PPI in any of the strains tested. A second form of postnatal stress (repeated footshock) also failed to alter PPI in the one strain studied, C57BL/6J. Present results demonstrate that the form of MS studied herein does not provide a robust model of early life stress effects on PPI in the mouse strains tested. The development and validation of a reliable mouse model of early life stress remains an important research goal.
Brain Research, 2011
Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the 14 C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility ('freezing'). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, nucleus acumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation.