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The response pattern of noradrenaline release to repeated stress in the hypothalamic paraventricular nucleus differs according to the form of stress in rats.

The effect of two repeated forms of stress, manual restraint and tail-pinch, on noradrenaline (NA) release in the hypothalamic paraventricular nucleus of the rat was examined by intracerebral microdialysis. Manual restraint significantly increased NA release, but the stimulatory effect gradually declined when the stress was repeated at intervals of 120 min. High K+ induced a great increase in NA release even when manual restraint produced no significant effect on NA release. In contrast, tail-pinch significantly increased NA release to a greater extent than manual restraint, and the increase in NA release did not change when the stress was repeated three times at intervals of 120 min. These results suggest that desensitization of NA neurons ending in the hypothalamic paraventricular nucleus occurs in response to painless stress, such as manual restraint, whereas no attenuation of NA release is caused by repeated stress accompanied by pain, such as tail-pinch.

Animals↗

Combat stress reactions, post traumatic stress disorder and somatic complaints among Israeli soldiers.

This study examined the effect of combat stress on somatic health in a sample of 804 Israeli soldiers. Three groups of subjects were assessed: combatants who did not participate in the Lebanon War, combatants who fought and suffered from combat stress reactions, and combatants who participated in the Lebanon War but did not sustain psychiatric injury. One year following the war subjects were asked to report somatic complaints and were screened for post-traumatic stress disorder. Results indicated that participation in combat per se did not have pathogenic effects. However, combat stress reactions and post-traumatic stress disorder were found to be associated with somatic complaints. The practical and theoretical implications of these findings are discussed.

Adult↗

Prior stress and susceptibility to stress ulcer.

Rats were exposed to daily sessions of either restraint plus cold, forced exercise, or grid shock for one month and then subjected to the ulcerogenic effects of either supine restraint plus cold, or activity-stress. Chronic stress generally protected against stress ulcer but the protection depended on the degree of similarity between the pre-treatment stressor and the ulcerogenic procedure. Pre-treatment with restraint plus cold provided protection which applied not only to supine restraint plus cold but also generalized to activity-stress. Foot-shock pre-treatment did not significantly reduce restraint ulcer but it significantly exacerbated activity-stress ulcer.

Animals↗

Prenatal stress attenuates ulceration in the activity stress paradigm.

In the present study, 28 pregnant rats were subjected to either light-restraint stress or no manipulation for days 14-21 of the gestational period. At approx. 50 days of age, both male (n = 16) and female (n = 16) prenatally stressed (PS) and control offspring were subjected to the activity stress (AS) paradigm. During this subsequent stress experience, PS rats developed less ulceration than control rats. PS rats also displayed about half the activity of the control animals during the habituation phase of the AS paradigm, prior to the induction of stress. Given this decrease in baseline activity in PS animals, implications of using activity as a measure of emotionality in PS animals are discussed. Several sex differences were also observed; females differed from males in that they 1) exhibited higher activity levels in both the habituation and experimental phases of the AS procedure, 2) developed heavier relative adrenal weights, and 3) reached criteria for sacrifice in fewer days.

Adrenal Glands↗

Effects of stress on drug-induced yawning: constant vs. intermittent stress.

Effects of stress on drug-induced yawning: Constant vs. intermittent stress. PHYSIOL BEHAV 58(1) 181-184, 1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimming would result in suppression of apomorphine-, pilocarpine-, and physostigmine-induced yawning. Immobilization caused suppression of yawning, whereas foot shock and swimming resulted in increased number of yawns. Since interstressor interval was long in the two latter stressors, animals could have recovered and the increase in yawning could be due to the last (acute) exposure to stress. In Experiment 2 we recorded the number of yawns induced by pilocarpine in animals exposed to 1 h of swimming or foot shock. No differences between control and acutely stressed animals were detected. These results suggest that yawning is differently altered by constant and intermittent stressors (i.e., diminished by constant and increased by intermittent stress).

Animals↗

Effects of ethanol on locomotor depression and corticosterone release induced by restraint-stress: support for a stress-ethanol interaction.

The interaction between restraint-stress and ethanol was investigated in the rat. The effects of ethanol pretreatment (0.0, 1.0, 1.5, 2.0 g/kg, 20% v/v) on locomotor depression and corticosterone release induced by restraint-stress (15, 60 min) were measured. Restraint durations of 15, 30, 90 and 120 min were found to decrease locomotor activity while animals restrained for 60 min did not differ from home cage controls. All restraint durations induced a significant increase in plasma levels of corticosterone. Locomotor activity counts of ethanol-pretreated (1.0, 1.5, 2.0 g/kg; 20% v/v) animals restrained for 15 min were not found to be lower than those of ethanol-pretreated animals remaining in home cages. Ethanol pretreatment did not differentially affect the locomotor activity of restrained or home cage animals in the 60-min condition. Plasma corticosterone levels of ethanol-pretreated animals restrained for 15 min were identical to those of ethanol-pretreated home cage controls. However, ethanol-pretreated animals restrained for 60 min demonstrated plasma corticosterone levels higher than those obtained by ethanol pretreatment or 60-min restraint alone. Blood ethanol levels were not found to be different between ethanol-control and ethanol-stress animals. These results provide support for a stress-ethanol interaction. They also suggest a differential interaction of ethanol with different intensities of stress.

Animals↗

The cycle of stress--a circular model for the psychobiological response to strain and stress.

A circular model is presented for the stress reaction. The model is composed of four phases that follow successively one after the other. The circular model which is called the stress cycle incorporates various concepts and terminologies that traditionally have been used in the stress field. The uniqueness of this stress cycle is that it will enable researchers to quantitate several parameters of the cycle such as the frequency, the amplitude and duration of the cycle. The importance of these parameters for stress management education and coping mechanisms are discussed.

Humans↗

The additional prognostic value of coronary flow reserve on left anterior descending artery in patients with negative stress echo by wall motion criteria. A Transthoracic Vasodilator Stress Echocardiography Study.

BACKGROUND: Vasodilator stress echocardiography allows imaging of left anterior descending (LAD) coronary flow reserve (CFR), which may provide additional prognostic information over regional wall motion. AIM: To assess the prognostic value of CFR in patients with known or suspected coronary artery disease (CAD) and negative stress echo. METHODS: We studied 329 consecutive patients (193 men, age 61 +/- 13 years) with known (n = 101) or suspected (n = 228) CAD and negative stress echo by standard wall motion criteria. All patients underwent dipyridamole (up to 0.84 mg/kg in 10 minutes) stress echo with CFR evaluation of LAD by Doppler. RESULTS: During follow-up (28 +/- 10 months), 22 events occurred: 1 cardiac death, 6 nonfatal myocardial infarctions, 5 unstable anginas, and 10 late (> 6 months) coronary revascularizations. Moreover, 9 patients underwent early (< 6 months) revascularization and were censored. Using a receiver operating characteristic analysis, CFR < or = 1.92 was the best predictor of future events (area under the curve = 0.80, sensitivity = 77%, specificity = 85%) and was taken as criterion for reduced CFR accordingly. Sixty-three (19%) patients had reduced and 266 (81%) had normal CFR on LAD. The 36-month event-free survival was higher in patients with normal and lower in patients with reduced CFR (98% vs 64%, P < .0001). At Cox analysis, CFR of LAD (hazard ratio [HR] 16.52, 95% CI 5.76-47.40, P < .0001), left ventricular mass index (HR 1.03 per unit increment, 95% CI 1.00-1.05, P = .01), and smoking habit (HR 3.00, 95% CI 1.24-7.23, P = .01) were independent prognostic indicators. Using an interactive stepwise procedure, CFR on LAD provided additional prognostic information to clinical, resting echo, and angiographic findings. CONCLUSIONS: In patients with known or suspected CAD and negative stress echocardiography by wall motion criteria, CFR provides independent information for prognostic stratification, and a reduced CFR is associated with a less benign long-term outcome.

Coronary Artery Disease↗

Social stress profoundly affects lipid metabolism: over-expression of SR-BI in liver and changes in lipids and lipases in plasma and tissues of stressed mice.

We examined the effect of chronic social stress, similar to that endured by humans, on lipid metabolism of mice. The activity of the lipoprotein lipase (LPL) enzyme increased in adrenals, while in plasma it diminished significantly. Hepatic lipase (HL) was strongly affected in liver and adrenal glands, increasing four-fold and three-fold, respectively. At the same time, scavenger receptor class-B type-I (SR-BI), which are considered the high-density lipoprotein (HDL) receptor in the liver, increased significantly. Although the adrenals do not synthesise HL, the increase in HL may facilitate the uptake of HDL cholesterol for the synthesis of corticoids, which increase significantly following chronic stress. The volume of adrenal glands in control animals was significantly higher than in stressed animals (1.23+/-0.12 mm3 versus 0.29+/-0.06 mm3, p<0.001), corresponding with the weight difference of these organs. Medulla volume was also different in the two groups (0.27+/-0.10 mm3 versus 0.04+/-0.02 mm3, p<0.05). Despite this, corticosterone in plasma was significantly higher in stressed animals. Our results shows, for the first time, the effect of chronic social stress on lipid metabolism in general, and in particular on the SR-BI receptor and HL, which is directly involved in cholesterol reverse transport.

Adrenal Cortex Hormones↗

Stress susceptibility predicts the severity of immune depression and the failure to combat bacterial infections in chronically stressed mice.

Chronic psychological stress has been suggested to play a role in disorders in which the immune system unexpectedly fails to respond in a protective manner. Chronic combined acoustic and restraint stress compromises the anti-bacterial defense mechanisms of female BALB/c mice. The immunodeficiency is characterized by an apoptotic loss of lymphocytes, reduced ex vivo-inducibility of TNF but increased inducibility of IL10, reduced T-cell proliferation, and impaired phagocyte functions. Stressed mice develop depression-like behavior that was monitored by a stress severity score (SSS). Besides a strain (BALB/c>CBA) and gender (male>female) dependent susceptibility to chronic stress, inbred mice have an individual coping ability. Importantly, the individual SSS strongly correlates with Escherichia coli dissemination after infection as well as with IL10-inducibility and circulating corticosterone levels of each animal.

Acoustic Stimulation↗

Impact of stress reduction instructions on stress and cortisol levels during pregnancy.

This pilot study examined whether giving stress reduction (SR) instructions to pregnant women would be effective in regulating stress, mood, and cortisol levels during pregnancy. Forty-one predominantly low-income Latina women, receiving prenatal services at a public county hospital, completed measures of stress and mood (depressive symptoms, positive and negative affect) and provided morning and evening saliva samples to measure cortisol prior to and after receiving SR instructions. We hypothesized that adherence to these SR instructions would result in lower levels of stress, negative mood states, and cortisol levels when compared to baseline values. Repeated measures ANOVA analyses demonstrated significantly lower levels of stress (P < 0.001), lower symptoms of depression and negative affect (P < 0.001), and lower levels of morning cortisol (P = 0.01) under the SR condition, compared to baseline. Health behaviors that were engaged in during the SR condition and implications for prenatal health interventions are discussed.

Adolescent↗

Exposure to predator odor stress increases efflux of frontal cortex acetylcholine and monoamines in mice: comparisons with immobilization stress and reversal by chlordiazepoxide.

Psychogenic stress may be associated with the development of mood disorders and schizophrenia. The frontal cortex (FC) regulates stress responses, and its dysfunction contributes to certain neuropsychiatric disorders. We tested the effects of exposure to predator odor stress (POS), a psychogenic stressor, on the concurrent efflux of four major neurotransmitters within the FC in mice in comparison to immobilization stress (IMS), a physical/systemic stressor. POS and IMS significantly increased efflux of acetylcholine (ACh), serotonin (5-HT) and dopamine (DA), but not norephinephrine, within the FC. POS produced a somewhat longer-lasting efflux of 5-HT, as compared to IMS. The effects of POS and IMS on ACh, 5-HT and DA were blocked by chlordiazepoxide. Overall, we demonstrate a novel method to measure the effects of distinctly different stress modalities on FC neurotransmission and suggest that FC responsivity to stressors may be an important marker for evaluating anxiolytic drugs.

Acetylcholine↗

Husbandry stress during early life stages affects the stress response and health status of juvenile sea bass, Dicentrarchus labrax.

In aquaculture management it is important to establish objective criteria to assess health and welfare of the fish. Here we show that European sea bass (Dicentrarchus labrax) confronted with husbandry-associated stress (tank cleaning, i.e. scrubbing, and water temperature variation) during early life stages show poorer survival and disease resistance as juveniles. We evaluated several parameters for stress (plasma cortisol, glucose and lactate, hydromineral status), growth performance, the immune response (plasma IgM levels) and the effects of a nodavirus challenge. Principal component analysis allowed the establishment of a stress panel including plasma cortisol, osmolality, IgM levels and weight. Sea bass juveniles reared during early life in high and constant temperature perform best in terms of stress-related parameters assessed by principle component analysis. Variable water temperature triggers dramatic changes in plasma cortisol, osmolality, IgM levels, body weight and susceptibility to nodavirus that suggest a strong and prolonged activation of the HPI axis. Scrubbing induces some disturbances typical for mild short-term, acute stress, viz. increased plasma osmolality and decreased IgM levels, but does not affect plasma cortisol, growth or susceptibility to nodavirus of sea bass. Our data fit well with the concept of allostasis. We discuss the relevance of our work for sea bass aquaculture.

Animal Husbandry↗

Stress-management methods of the community-dwelling elderly in Hong Kong: implications for tailoring a stress-reduction program.

This study aims to explore the preferences of the elderly in adopting five stress-management methods and to identify the reasons for nonadoption. A convenience sample of 212 community-dwelling elders age 60 or older was obtained from four multiservice centers for the elderly in Hong Kong. The findings suggest that the elderly prefer to manage stress on their own rather than rely on social support from family, friends, and professionals. The notion of saving face in the Chinese culture and an inadequate supply of social support are possible explanations why the elderly do not like to seek help from others to reduce stress. This study offers a model for a stress-reduction program for community-dwelling elderly people in Hong Kong to enhance their ability to cope with stress.

Adaptation, Psychological↗

Age-related and regional differences in the stress-strain and stress-relaxation behaviours of the rat incisor periodontal ligament.

Groups of rats were killed at 2, 6, 12, and 24 months of age. From dissected left and right mandibles in each rat, three pairs of transverse sections were cut at the incisal, middle, and basal regions of the incisor. One section in each pair was loaded until failure and a stress-strain curve for the periodontal ligament (PDL) was obtained. The other section was loaded to up to 50% of the maximum shear stress as determined from the contralateral section and then kept at a constant strain for 10 min, to obtain the stress-relaxation curve at the same region of the PDL. The maximum shear stress and toughness increased with age at the incisal region and the maximum shear strain increased with age at the incisal and middle regions. The tangent modulus decreased with advancing age at the middle region. The stress-relaxation during 10 min decreased with advancing age at the incisal and basal regions, but not at the middle region. The relaxation process was well described by a sum of three exponential decay functions, reflecting the short-, medium-, and long-term relaxation components. The age-related decrease in the relaxation was mainly attributable to increases in the ratio and relaxation time of the long-term relaxation component. These results suggest that with advancing age the mechanical strength and toughness of the PDL are enhanced mostly at the incisal region and that the viscous fraction is relatively decreased at the incisal and basal regions along the long axis of the rat incisor.

Aging↗

Effects of repeated tianeptine treatment on CRF mRNA expression in non-stressed and chronic mild stress-exposed rats.

Accumulating evidence suggests that dysregulation of corticotropin-releasing factor (CRF) may play a role in depression and that this dysregulation may be corrected by antidepressant drug treatment. Here, we examined whether chronic mild stress (CMS) alters CRF mRNA levels in stress-related brain areas including the bed nucleus of the stria terminalis (BNST) and the central nucleus of amygdala (CeA), and whether repeated tianeptine treatment can attenuate CMS-induced changes in CRF mRNA levels. Male rats were exposed to CMS for 19 days, and control animals were subjected to brief handling. Both groups were injected daily with tianeptine or saline. CMS significantly increased CRF mRNA levels in the dorsal BNST (dBNST), but not in other areas. Repeated tianeptine treatment prevented the CMS-induced increase in CRF mRNA levels in the dBNST, and reduced CRF mRNA levels in dBNST in non-stressed controls. Moreover, repeated tianeptine treatment significantly decreased CRF mRNA levels in the ventral BNST and CeA of non-stressed controls as well as CMS-exposed rats. These results show that CMS induces a rather selective increase of CRF mRNA in the dBNST. In addition, these results suggest that repeated tianeptine treatment diminishes the basal activity of CRF neurons and reduces their sensitivity to stress.

Animals↗

Habituation to repeated restraint stress is associated with lack of stress-induced c-fos expression in primary sensory processing areas of the rat brain.

Rats repeatedly exposed to restraint show a reduced hypothalamic-pituitary-adrenal axis response upon restraint re-exposure. This hypothalamic-pituitary-adrenal axis response habituation to restraint does not generalize to other novel stressors and is associated with a decrease in stress-induced c-fos expression in a number of stress-reactive brain regions. We examined whether habituation to repeated restraint is also associated with adaptation of immediate early gene expression in brain regions that process and relay primary sensory information. These brain regions may not be expected to show gene expression adaptation to repeated restraint because of their necessary role in experience discrimination. Rats were divided into a repeated restraint group (five 1-hour daily restraint sessions) and an unstressed group (restraint naïve). On the sixth day rats from each group were either killed with no additional stress experience or at 15, 30 or 60 min during restraint. Immediate early gene expression (corticotrophin-releasing hormone heteronuclear RNA, c-fos mRNA, zif268 mRNA) was determined by in situ hybridization. A reduction in stress-induced hypothalamic-pituitary-adrenal axis hormone secretion (plasma corticosterone and adrenocorticotropic hormone) and immediate early gene expression levels in the paraventricular nucleus of the hypothalamus, the lateral septum and the orbital cortex was observed in repeated restraint as compared with restraint naïve animals. This reduction was already evident at 15 min of restraint. Unexpectedly, we also found in repeated restraint rats a reduction in restraint-induced c-fos expression in primary sensory-processing brain areas (primary somatosensory cortex, and ventroposteriomedial and dorsolateral geniculate nuclei of thalamus). The overall levels of hippocampal mineralocorticoid receptor heteronuclear RNA or glucocorticoid receptor mRNA were not decreased by repeated restraint, as may occur in response to severe chronic stress. We propose that repeated restraint leads to a systems-level adaptation whereby re-exposure to restraint elicits a rapid inhibitory modulation of primary sensory processing (i.e. sensory gating), thereby producing a widespread attenuation of the neural response to restraint.

Afferent Pathways↗

Endocrine stress responses in TH1-mediated chronic inflammatory skin disease (psoriasis vulgaris)--do they parallel stress-induced endocrine changes in TH2-mediated inflammatory dermatoses (atopic dermatitis)?

In previous research we reported attenuated responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis and further, an increased reactivity of the sympathetic adrenomedullary (SAM) system to stress in patients suffering from atopic dermatitis (AD). AD is a chronic inflammatory skin disease mainly triggered by TH(2)-dependent inflammatory processes. The specific goal of the present study was to investigate whether altered HPA axis and SAM system responsiveness to stress can also be found in TH(1)-mediated inflammatory conditions. Patients with psoriasis (PSO; n=23), a TH(1)-mediated inflammatory (autoimmune) skin disease and healthy controls (n=25) were exposed to a standardized laboratory stressor (TSST) which mainly consists of a free speech and a mental arithmetic task in front of an audience. To investigate HPA axis and SAM system responsiveness, cortisol, ACTH, and catecholamines were determined before and after the stress test. In addition, cortisol levels after awakening and cortisol levels during the day (short diurnal profile) were determined. In order to test feedback sensitivity of the HPA axis, a dexamethasone (DEX) suppression test (0.5 mg) was performed. Analysis of cortisol and ACTH levels after the stress test yielded no significant differences between PSO subjects and controls indicating no altered HPA axis function in this patient group. Further, no between-group differences were found in cortisol levels after awakening or during the day (short diurnal profile). Additionally, no difference between PSO and healthy subjects in the feedback sensitivity of the system could be found (DEX test). However, PSO patients showed elevated epinephrine (F(3,102)=4.7; p<0.005) and norepinephrine (F(3,135)=2.7; p<0.05) levels in response to the stress test when compared to the controls. These findings suggest no altered HPA axis responsiveness, but increased reactivity of the SAM system in TH(1)-mediated chronic inflammatory skin disease.

Adrenal Medulla↗