Gestational chronic mild stress: effects on acoustic startle in male offspring of rats.

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.

Influence of diurnal phase on startle response in adult rats exposed to dexamethasone in utero.

Depression and pathological anxiety disorders are among the most prevalent neurological diseases in the world and can be precipitated and exacerbated by stress. Prenatal stress alters both behavioral and endocrine responses to stressful stimuli in later life. We have previously observed increased basal acoustic startle response (ASR) in Wistar rats exposed to stress or dexamethasone (DEX) in utero when tested during the light phase of the circadian rhythm, and decreased prepulse inhibition (PPI) in similar animals tested during the dark phase of the cycle. We speculated that this observation of increased basal startle might be influenced by diurnal phase. In the present study, adult female Sprague Dawley rats, stressed prenatally with DEX (200 µg/kg, gestational days 14-21) and postnatally by blood sampling under restraint, were tested for the ASR during both circadian phases (light and dark). Basal startle was increased in animals tested both during the light and the dark phases of the cycle. We hereby replicated our earlier findings in a new strain and laboratory, thus strengthening the validity of our model regarding prenatal stress effects on ASR in female offspring. Our results indicate that observation of increased basal ASR is not solely dependent on diurnal phase. We found no difference in hippocampal glucocorticoid and mineral corticoid receptor expression between groups.

Reduced mobility but unaffected startle response in female rats exposed to prenatal dexamethasone: different sides to a phenotype.

An adverse fetal environment is strongly associated with behavioral and emotional development in later life, and environmental interactions with the genome are essential in the development of pathophysiology. This implicates that a genetic vulnerability or other predisposition may interact with the environment and stressful life events to trigger mental disease. The startle reflex is highly sensitive to fear and anxiety in humans and animals. Elevated startle magnitude has been proposed as a marker for neurodevelopmental disorders. We have recently established an animal model for possible development of anxiety, where female rats are exposed to two stressful life events, during prenatal life and as adolescents, respectively. A blood sampling procedure 3 months prior to startle testing has previously been found to increase basal startle, but only in prenatally stressed rats. As the experimental procedure of acoustic startle response (ASR) measurement resembles the aversive blood sampling procedure, this suggests that effects on ASR may be caused by aversive contextual similarities between blood sampling under restraint and the ASR test. In the present study, postnatal blood sampling was replaced by another dissimilar stressful event. Animals exposed to a high prenatal glucocorticoid level (i.e. 150 mug dexamethasone/kg) were statistically significantly more immobile in the forced swim test (FST) than animals exposed to a lower level of dexamethasone (50 mug/kg) and control animals. Exposure to a novel contextual stressor at 3 months of age (FST) was unassociated with changes in basal startle. These data suggest, since the high prenatal dexamethasone group showed increased immobility in the FST but coped equally well with controls in the ASR, that the outcome of environmental influences is determined by the individual circumstances as different situations require different coping abilities in the same individual.

Prenatal and adult stress interplay--behavioral implications.

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.