Showing papers on "Chronic stress published in 2000"

The neurobiology of stress and gastrointestinal disease

Abstract: The role of stress in the modulation of the most common gastrointestinal disorders has traditionally been considered a domain of psychology, and has frequently been lumped together with the role of psychiatric comorbidity. Among clinicians, the term “stress” is generally taken as synonymous with psychological (“exteroceptive”) stress. Based on the deeply ingrained Cartesian view in medicine and gastroenterology, stress and psychological factors have been considered fundamentally separate and unrelated to the “real” biological changes underlying organic disease. However, recent breakthroughs in the understanding of the neurobiology of the organism's response to acute and chronic stress, and the evolving understanding of elaborate brain-gut interactions and their modulation in health and disease, are beginning to require a reassessment of chronic stress in the pathophysiology and management not only of functional but also of “organic” gastrointestinal disorders. Certain stressful life events have been associated with the onset or symptom exacerbation in some of the most common chronic disorders of the digestive system, including functional gastrointestinal disorders (FGD), inflammatory bowel disease (IBD), gastro-oesophageal reflux disease (GORD), and peptic ulcer disease (PUD). Even though methodological differences in reported studies which do and do not support such an association remain to be resolved, the association of sustained stressful life events preceding symptom exacerbation is based on several well designed surveys in patients with FGD,1-4with post-infectious irritable bowel syndrome (IBS),4 and with IBD.5-8 In addition, acute life threatening stress episodes in adult life (rape, post-traumatic stress syndrome) are an important risk factor in the development of functional gastrointestinal disorders.9 Finally, early life stress in the form of abuse plays a major role in the susceptibility of individuals to develop functional as well as IBD10-14 later in life. Thus, depending on the type of stressor, the lag time between the stressful event …

Depression and sensitization to stressors among young women as a function of childhood adversity.

Abstract: The authors tested a stress-sensitization version of a diathesis-stress approach to depression. In a 2-year longitudinal follow-up design, exposure to stressful life events was examined in young women in the transition to adulthood. The authors hypothesized that those who had experienced one or more significant childhood adversities would have a lower threshold for developing a depressive reaction to stressors. Results indicated that women with exposure to one or more childhood adversities--such as family violence, parent psychopathology or alcoholism, and others--were more likely to become depressed following less total stress than women without such adversity. The results could not be accounted for by chronic stress or prior depression. Both biological and psychological sensitization mechanisms may be speculated to play a role, but the actual mechanisms of stress sensitization remain to be explored.

Chronic Stress Induces Impairment of Spatial Working Memory Because of Prefrontal Dopaminergic Dysfunction

Abstract: Although the mechanism responsible for cognitive deficits in stress-related neuropsychiatric disorders has been obscure, prefrontal cortical (PFC) dopaminergic dysfunction is thought to be involved. In animals, the mesoprefrontal dopaminergic system is particularly vulnerable to stress, and chronic stress induces working memory impairment. However, the relation between the working memory impairment and altered dopaminergic activity in chronically stressed rats is unclear. Furthermore, the change of dopaminergic activity in the PFC induced by stress is thought to express as a stress response, not as a disorder of organic function. We have previously reported that chronic stress administered by water immersion and restraint for 4 weeks induces a organic disorder such as hippocampal neuronal degeneration. We therefore examined whether chronically stressed (4 weeks) and recovered (10 d) rats show a working memory impairment caused by reduced dopamine (DA) transmission in the PFC, as suspected in the neuropsychiatric disorders. The stress impaired the spatial working memory evaluated by T-maze task and induced a marked reduction of DA transmission concomitant with an increase in DA D1 receptor density in the PFC. This memory impairment was sufficiently ameliorated by intra-PFC infusion of 10 ng SKF 81297, a D1 receptor-specific agonist. Pretreatment with intraperitoneal injection of 20 μg/kg SCH 23390, a D1 receptor antagonist, reversed the SKF 81297 response. These results indicate that chronic stress induces working memory impairment through a D1 receptor-mediated hypodopaminergic mechanism in the PFC. These findings provide important information for understanding of the mechanisms underlying PFC dysfunction in stress-related neuropsychiatric disorders.

Toward an interpersonal life-stress model of depression: the developmental context of stress generation.

Abstract: The validity of a developmentally based life-stress model of depression was evaluated in 88 clinic-referred youngsters. The model focused on (a) the role of child‐environment transactions, (b) the specificity of stress‐psychopathology relations, and (c) the consideration of both episodic and chronic stress. Semistructured diagnostic and life-stress interviews were administered to youngsters and their parents. As predicted, in the total sample child depression was associated with interpersonal episodic and chronic stress, whereas externalizing disorder was associated with noninterpersonal episodic and chronic stress. However, the pattern of results differed somewhat in boys and girls. Youngsters with comorbid depression and externalizing disorder tended to experience the highest stress levels. Support was obtained for a stress-generation model of depression, wherein children precipitate stressful events and circumstances. In fact, stress that was in part dependent on children’s contribution distinguished best among diagnostic groups, whereas independent stress had little discriminative power. Results suggest that life-stress research may benefit from the application of transactional models of developmental psychopathology, which consider how children participate in the construction of stressful environments.

Stress and body shape: Stress-induced cortisol secretion is consistently greater among women with central fat.

Abstract: Objective Excessive central fat puts one at greater risk of disease. In animal studies, stress-induced cortisol secretion has been shown to increase central fat. The objective of this study was to assess whether women with central fat distribution (as indicated by a high waist-to-hip ratio [WHR]), across a range of body mass indexes, display consistently heightened cortisol reactivity to repeated laboratory stressors. Methods Fifty-nine healthy premenopausal women, 30 with a high WHR and 29 with a low WHR, were exposed to consecutive laboratory sessions over 4 days (three stress sessions and one rest session). During these sessions, cortisol and psychological responses were assessed. Results Women with a high WHR evaluated the laboratory challenges as more threatening, performed more poorly on them, and reported more chronic stress. These women secreted significantly more cortisol during the first stress session than women with a low WHR. Furthermore, lean women with a high WHR lacked habituation to stress in that they continued to secrete significantly more cortisol in response to now familiar challenges (days 2 and 3) than lean women with a low WHR. Conclusions Central fat distribution is related to greater psychological vulnerability to stress and cortisol reactivity. This may be especially true among lean women, who did not habituate to repeated stress. The current cross-sectional findings support the hypothesis that stress-induced cortisol secretion may contribute to central fat and demonstrate a link between psychological stress and risk for disease.

Chronic social stress reduces dendritic arbors in CA3 of hippocampus and decreases binding to serotonin transporter sites.

Abstract: Male rats housed in mixed-sex groups in a visible burrow system (VBS) form a dominance hierarchy in which subordinate animals show stress-related changes in behavior, endocrine function and neurochemistry. Dominants also appear to be moderately stressed compared to controls, although these animals do not develop the more pronounced behavioral and physiological deficits seen in the subordinates. In the present study, we examined the effects of chronic psychosocial stress on the morphology of Golgi-impregnated CA3 pyramidal neurons. In addition, since serotonin has been implicated in the mechanisms mediating the dendritic remodeling seen with other chronic stress regimens, we used quantitative autoradiography to measure binding to the serotonin transporter (5HTT) in hippocampus and dorsal and median raphe. Chronic social stress led to a decrease in the number of branch points and total dendritic length in the apical dendritic trees of CA3 pyramidal neurons in dominant animals compared to unstressed controls; subordinates also had a decreased number of dendritic branch points. [(3)H]paroxetine binding to the 5HTT was decreased in Ammon's horn in both dominants and subordinates compared to controls, while 5HTT binding remained unchanged in dentate gyrus and raphe. The similarity of the changes in 5HTT binding and dendritic arborization between both groups of VBS animals, despite apparent differences in stressor severity, suggests that these changes may be part of the normal adaptive response to chronic social stress. The mechanisms underlying dendritic remodeling in CA3 pyramidal neurons are likely to involve stress-induced changes in glucocorticoids and in 5HT and other transmitters.

Treadmill running produces both positive and negative physiological adaptations in Sprague-Dawley rats.

Abstract: Exercise training produces a vast array of physiological adaptations, ranging from changes in metabolism to muscle mitochondrial biogenesis. Researchers studying the physiological effects of exercise often use animal models that employ forced exercise regimens that include aversive motivation, which could activate the stress response. This study examined the effect of forced treadmill running (8 wk) on several physiological systems that are sensitive to training and stress. Forced treadmill running produced both positive and negative physiological adaptations. Indicative of positive training adaptations, exercised male Sprague-Dawley rats had a decrease in body weight gain and an increase in muscle citrate synthase activity compared with sedentary controls. In contrast, treadmill running also resulted in the potentially negative adaptations of adrenal hypertrophy, thymic involution, decreased serum corticosteroid binding globulin, elevated lymphocyte nitrite concentrations, suppressed lymphocyte proliferation, and suppressed antigen-specific IgM. Such alterations in neuroendocrine tissues and immune responses are commonly associated with chronic stress. Thus treadmill running produces both positive training adaptations and potentially negative adaptations that are indicative of chronic stress. Researchers employing forced activity need to be aware that this type of exercise procedure also produces physiological adaptations indicative of chronic stress and that these changes could potentially impact other measures of interest.

The role of stress in the pathophysiology of the dopaminergic system

Abstract: In this review, we will examine the most recent preclinical evidence in support of the fact that both acute and chronic stress may have a detrimental impact on the normal function of the dopaminergic system. In recent decades, the term stress has changed its meaning from that of a 'non-specific body response' to a 'monitoring system of internal and external cues'; that is a modality of reaction of the mammalian central nervous system (CNS) which is critical to the adaptation of the organism to its environment. Compelling results have demonstrated that the dopaminergic system is important not only for hedonic impact or reward learning but also, in a broader sense, for reactivity to perturbation in environmental conditions, for selective information processing, and for general emotional responses, which are essential functions in the ability (or failure) to cope with the external world. In this, stress directly influences several basic behaviors which are mediated by the dopaminergic system such as locomotor activity, sexual activity, appetite, and cross sensitization with drugs of abuse. Studies using rat lines which are genetically different in dopamine (DA) physiology, have shown that even small alterations in the birth procedure or early life stress events may contribute to the pathophysiology of psychiatric disorders-in particular those involving central DA dysfunction-and may cause depression or psychotic derangement in the offspring. Finally, the fact that the dopaminergic system after stress responds, preferentially, in the medial prefrontal cortex (MFC), is thought to serve, in humans, as a protection against positive psychotic symptoms, since the increased DA activity in the MFC suppresses limbic DA transmission. However, excessive MFC dopaminergic activity has a negative impact on the cognitive functions of primates, making them unable to select and process significant environmental stimuli. Thus it appears that a critical range of DA turnover is necessary for optimal cognitive functioning after stress, in the response of the CNS to ever-changing environmental demands. Molecular Psychiatry (2000) 5, 14-21.

Behavioural and hormonal indicators of enduring environmental stress in dogs

Abstract: Animal Welfare 2000, 9: 49-62 Four groups of dogs, which had been subjected to housing conditions of varying quality for years, were assumed to experience different levels of stress. The groups were compared for behavioural and hormonal parameters in order to identifY measures that indicate chronic stress in the dog and which may help to identifY poor welfare in this species. As a standard for comparison, one of the four groups was composed of privately owned dogs; we assumed that chronic stress levels were relatively low in this group (GI). The three remaining groups of dogs (GIl, GIIl and GIV) were kept under conditions of low to relatively high austerity, and had basal urinary ratios of cortisol to creatinine, adrenaline to creatinine and, to a lesser extent, noradrenaline to creatinine, that varied from low to high, respectively. Significant differences (P < 0.05) were found in cortisol to creatinine ratios when comparing GI to GIl, GIll and GIV and when GIl was compared to GIV. Statistical analyses indicated that the mean adrenaline to creatinine ratio in GI differed from that in the remaining groups and that the ratio in GIl differedfrom that in GIll Noradrenaline to creatinine ratios differed significantly only between GI and GIll Dopamine to creatinine ratios and noradrenaline to adrenaline ratios did not differ significantly between groups. When dogs were not disturbed, those that were kept under the most austere conditions typically had high levels of locomotor activity, nosing, urinating and paw lifting. After mild disturbance by a slamming door or in the presence of a researcher these animals reacted actively, with increased locomotor activity, circling and nosing, and they showed high levels of behaviours that have previously been associated with acute stress: body shaking, yawning, ambivalent postures and displacement behaviours. Chronic stress in dogs may be identified by increased paw lifting when animals are not disturbed and by ample behavioural expressions of arousal when they are mildly stimulated. Since some behaviours may occur in contexts not related to stress, behavioural data are easily misinterpreted with regard to chronic stress. Interpretation will only be meaningful when physiological measures such as urinary adrenaline to creatinine ratios and, especially, urinary cortisol to creatinine ratios are also determined.

Chronic stress impairs rat growth and jejunal epithelial barrier function: role of mast cells

Abstract: We examined the impact of chronic stress on rat growth rate and intestinal epithelial physiology and the role of mast cells in these responses. Mast cell-deficient (Ws/Ws) rats and +/+ littermate c...

Chronic Restraint Stress Promotes Lymphocyte Apoptosis by Modulating Cd95 Expression

Abstract: Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it is well established that stress alters the release of various hormones and neurotransmitters, the mechanisms by which stress affects immune responses remain elusive. We report here that mice subjected to chronic 12-hour daily physical restraint for two days exhibited a significant reduction in splenocytes, a process likely mediated by apoptosis as demonstrated by the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling assay. CD95 (Fas/APO-1) expression in splenic lymphocytes of stressed mice was substantially increased. Interestingly, Fas-immunoglobulin fusion protein and blocking antibodies against CD95 ligand inhibit stress-induced reduction in lymphocytes. The stress-induced changes in CD95 expression and lymphocyte number could be blocked by naltrexone or naloxone, specific opioid receptor antagonists, indicating a pivotal role of endogenous opioids in this process. In addition, the reduction of splenocytes in this model system seems to be independent of the hypothalamo-pituitary-adrenal axis, as both adrenalectomized and sham-operated mice exhibited similar responses to chronic stress. Moreover, chronic physical restraint failed to induce a decrease in lymphocyte numbers in CD95-deficient (Faslpr/lpr) mice. Therefore, stress modulates the immune system through CD95-mediated apoptosis dependent on endogenous opioids.

Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice.

Abstract: To dissect the effects of corticosteroids mediated by the mineralocorticoid (MR) and the glucocorticoid receptor (GR) in the central nervous system, we compared MR–/– mice, whose salt loss syndrome was corrected by exogenous NaCl administration, with GR–/– mice having a brain-specific disruption of the GR gene generated by the Cre/loxP-recombination system. Neuropathological analyses revealed a decreased density of granule cells in the hippocampus of adult MR–/– mice but not in mice with disruption of GR. Furthermore, adult MR–/– mice exhibited a significant reduction of granule cell neurogenesis to 65% of control levels, possibly mediated by GR due to elevated corticosterone plasma levels. Neurogenesis was unaltered in adult mice with disruption of GR. Thus, we could attribute long-term trophic effects of adrenal steroids on dentate granule cells to MR. These MR-related alterations may participate in the pathogenesis of hippocampal changes observed in ageing, chronic stress and affective disorders.

Occupational status, cortisol secretory pattern, and visceral obesity in middle-aged men.

Abstract: Objective: Despite several studies indicating that social gradients are predictive of cardiovascular mortality, the pathogenetic mechanisms remain incompletely understood. Research Methods and Procedures: A population sample of 51-year-old men (N = 284) was divided into a socioeconomic gradient with manual laborers, civil servants, and university graduates. Anthropometric measurements were registered. Cortisol concentrations were measured in saliva, collected repeatedly during an ordinary working day, and a low-dose dexamethasone suppression test was performed. Results: Lower socioeconomic status was associated with visceral obesity and higher cortisol values in relation to perceived stress. However, total cortisol secretion over the day of study was not elevated. The regulation of cortisol secretion showed less plasticity and dexamethasone inhibition was less efficient in the men in the lower socioeconomic status group than in those with a higher socioeconomic status. These are known consequences of long term stress. Longer duration in low socioeconomic conditions seemed to worsen these phenomena. Discussion: It was concluded that a low socioeconomic status is associated with perturbed cortisol secretion, which is elevated in relation to perceived stress. When the hypothalamic-pituitary-adrenal axis is subjected to prolonged increases in cortisol elicited by chronic stress, the regulation of cortisol secretion is affected, indicating neuroendocrine dysregulations. These observations may provide a means for understanding the association of socioeconomic impairments with visceral obesity and the social inequality in risk for prevalent and serious diseases.

A cholecystokinin-mediated pathway to the paraventricular thalamus is recruited in chronically stressed rats and regulates hypothalamic-pituitary-adrenal function.

Abstract: Chronic stress alters hypothalamic-pituitary-adrenal (HPA) responses to acute, novel stress. After acute restraint, the posterior division of the paraventricular thalamic nucleus (pPVTh) exhibits increased numbers of Fos-expressing neurons in chronically cold-stressed rats compared with stress-naive controls. Furthermore, lesions of the PVTh augment HPA activity in response to novel restraint only in previously stressed rats, suggesting that the PVTh is inhibitory to HPA activity but that inhibition occurs only in chronically stressed rats. In this study, we further examined pPVTh functions in chronically stressed rats. We identified afferent projections to the pPVTh using injection of the retrograde tracer fluorogold. Of the sites containing fluorogold-labeled cells, neurons in the lateral parabrachial, periaqueductal gray, and dorsal raphe containing fluorogold also expressed cholecystokinin (CCK) mRNA. We then examined whether these CCKergic inputs to the pPVTh were involved in HPA responses to acute, novel restraint after chronic stress. We injected the CCK-B receptor antagonist PD 135,158 into the PVTh before restraint in control and chronically cold-stressed rats. ACTH responses to restraint stress were augmented by PD 135,158 only in chronically stressed rats but not in controls. In addition, CCK-B receptor mRNA expression in the pPVTh was not altered by chronic cold stress. We conclude that previous chronic stress specifically facilitates the release of CCK into the pPVTh in response to acute, novel stress. The CCK is probably secreted from neurons in the lateral parabrachial, the periaqueductal gray, and/or the dorsal raphe nuclei. Acting via CCK-B receptors in pPVTh, CCK then constrains facilitated ACTH responses to novel stress in chronically stressed but not naive rats. These results demonstrate clearly that chronic stress recruits a new set of pathways that modulate HPA responsiveness to a novel stress.

Protective and damaging effects of stress mediators: central role of the brain.

Abstract: The mind involves the whole body, and two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Stress is a condition of the mind-body interaction, and a factor in the expression of disease that differs among individuals. It is not just the dramatic stressful events that exact their toll, but rather the many events of daily life that elevate and sustain activities of physiological systems and cause sleep deprivation, overeating, and other health-damaging behaviors, producing the feeling of being “stressed out.” Over time, this results in wear and tear on the body, which is called “allostatic load,” and it reflects not only the impact of life experiences but also of genetic load, individual lifestyle habits reflecting items such as diet, exercise, and substance abuse, and developmental experiences that set life-long patterns of behavior and physiological reactivity. Hormones associated with stress and allostatic load protect the body in the short run and promote adaptation by the process known as allostasis, but in the long run allostatic load causes changes in the body that can lead to disease. The brain is the key organ of stress, allostasis, and allostatic load, because it determines what is threatening and therefore stressful, and also determines the physiological and behavioral responses. Brain regions such as the hippocampus, amygdala, and prefrontal cortex respond to acute and chronic stress by undergoing structural remodeling, which alters behavioral and physiological responses. Translational studies in humans with structural and functional imaging reveal smaller hippocampal volume in stress-related conditions, such as mild cognitive impairment in aging and prolonged major depressive illness, as well as in individuals with low selfesteem. Alterations in amygdala and prefrontal cortex are also reported. Besides pharmaceuticals, approaches to alleviate chronic stress and reduce allostatic load and the incidence of diseases of modern life include lifestyle change, and policies of government and business that would improve the ability of individuals to reduce their own chronic stress burden.

Stress, immune regulation, and immunity: applications for asthma.

Abstract: The neuroendocrine mediators reach the cells of the immune system either through the peripheral circulation or through direct innervation of lymphoid organs. Primary and secondary lymphoid organs are innervated by sympathetic nerve fibers. Lymphocytes and monocytes express receptors for several stress hormones, including CRH, ACTH, cortisol, norepinephrine, and epinephrine. Therefore, it is reasonable to conclude that the neuroendocrine hormones released during a stressful event could alter immune function and subsequently alter the course of immune-based diseases. The impact of psychological stress on immune function has been the subject of extensive research efforts. Using a variety of models from largely healthy humans undergoing various forms of natural and experimental stress models, stress has been associated with suppression of NK activity, mitogen- and antigen-induced lymphocyte proliferation and in vitro production of IL-2 and IFN-gamma. Psychological stress is also associated with a higher rate of in vivo hypoergy to common recall-delayed type hypersensitivity antigens. These studies have suggested that psychological stress suppresses various components of CMI responses. Also, data suggest that chronic stress does not simply suppress the immune system, but induces a shift in the type-1/type-2 cytokine balance toward a predominant type-2 cytokine response. Such a change would favor the inflammatory milieu characteristic of asthma and allergic diseases. Recent studies using well-controlled teenage asthmatic subjects demonstrated immunological changes (decreased NK cell cytotoxicity and cytokine alterations) in response to exam stress. These immune alterations are consistent with a cytokine milieu that could potentially worsen asthma. However, there were no changes in peak flow rates, self-report asthma symptoms, or medication use. The lack of correlation between stress and asthma symptoms may have been related to the timing of the visits in relation to the stressor, the duration of the stressor, disease severity, or a lack of accurate self-report data. Alternatively, stress-mediated exacerbations of asthma may require multiple alterations by stress, including cytokine dysregulation or vagal-mediated airway hyperresponsiveness. The rationale for stress management in asthma is based upon the notion that stress causes a change in immune balance that would favor asthma activity in susceptible individuals. This immune imbalance can be found in TH1/TH2 cytokine changes that occur with stress. Although it has not yet been demonstrated that stress can cause or directly influence the development of asthma, it is interesting to note that both the incidence and prevalence of asthma continue to increase and are higher in urban than in rural areas. Among other differences is the well-appreciated higher chronic stress levels associated with urban living.

Activity of the hypothalamic-pituitary-adrenal axis in different obesity phenotypes.

Abstract: Subjects with abdominal obesity are characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to a condition of 'functional hypercortisolism'. This appears to be the result of two distinct mechanisms. The first, which appears to be central in origin, is characterized by altered ACTH pulsatile secretory dynamics and by hyper-responsiveness of the HPA axis to different neuropeptides and acute or chronic stress events and, possibly, to selected dietary factors. The other appears to be located in the periphery, specifically the liver and visceral adipose tissue, and is characterized by supranormal cortisol production, whose paracrine and systemic effects remain unclear. It is suggested that increased exposure to cortisol of the body may play a fundamental role not only in the development of increased fat in abdominal/visceral depots, but also in determining all metabolic abnormalities closely related to the abdominal obesity phenotype.

Antioxidant activity of tannoid principles of Emblica officinalis (amla) in chronic stress induced changes in rat brain.

Abstract: Effect of tannoid principles emblicanin A, emblicanin B, punigluconin, and pedunculagin of E. officinalis was assessed on chronic unpredictable footshock-induced stress-induced perturbations in oxidative free radical scavanging enzymes in rat brain frontal cortex and striatum. Chronic stress, administered over a period of 21 days, induced significant increase in rat brain frontal cortical and striatal superoxide dismutase (SOD) activity, concomitant with significant reduction in catalase (CAT) and glutathione peroxidase (GPX) activity. The changes in the enzyme activities was accompanied by an increase in lipid peroxidation, in terms of augmented thiobarbituric acid-reactive products. Administration of Emblica tannoids (10 and 20 mg, po) for 21 days, concomitant with the stress procedure, induced a dose-related alteration in the stress effects. Thus, a tendency towards normalization of the activities of SOD, CAT and GPX was noted in both the brain areas, together, with reduction in lipid peroxidation. The results indicate that the reported antistress rasayana activity of E. officinalis may be, at least partly due to its tendency to normalize stress-induced perturbations in oxidative free radical scavenging activity, in view of the postulate that several stress-induced diseases, including the process of aging, may be related to accumulation of oxidative free radicals in different tissues.

Restraint stress - Differential cardiovascular responses in Wistar-Kyoto and spontaneously hypertensive rats

Abstract: —With the use of a restraint stress paradigm, both normotensive Wistar-Kyoto (WKY ) rats and spontaneously hypertensive rats (SHR) underwent acute (1-hour restraint in a Perspex tube), chronic (1-hour restraint for 10 consecutive days), or no-restraint (control) stress Rats experiencing chronic restraint were previously implanted with telemetric probes to measure heart rate and blood pressure Basal (prestress session) cardiovascular variables did not change during the course of the study (SHR: mean arterial pressure 129±1 mm Hg, heart rate 288±4 bpm; WKY rats: mean arterial pressure 103±1 mm Hg, heart rate 285±3 bpm) Restraint caused tachycardia and pressor responses in the WKY rats and SHR, but these effects were greater in the hypertensive strain The duration of restraint-induced tachycardia did not change in the WKY rats between acute and chronic stress; however, a graded reduction in the duration of restraint-induced tachycardia occurred in the SHR, decreasing to WKY rat levels by day 7 of the 10-day regimen These data indicate that although the WKY rats can effectively “cope” within a single period of restraint, the coping mechanism is apparently impaired in the SHR compared with the WKY rats A reduced capacity to cope with processive stressors may thus have an affect on cardiovascular regulation and represent an additional risk factor in hypertension

Differential stress responsivity in diet-induced obese and resistant rats.

Abstract: The relationship between stress and obesity was assessed in male rats selectively bred to develop either diet-induced obesity (DIO) or diet resistance (DR) when fed a high-energy, 31% fat diet for 3 wk followed by 2 wk on a hyperphagic liquid diet (Ensure). One-half of the rats of each phenotype were subjected to moderate daily, unpredictable stress (cage changing, exposure to conspecific, swim, and immobilization stress, intraperitoneal saline injection) during the 5 wk. Both stressed and unstressed DIO rats were 26% heavier and ate 27% more than comparable DR rats at onset and had 48% lower basal morning plasma corticosterone levels. Stressed DR rats gained less weight and had significant elevations of basal morning corticosterone but reduced basal sympathetic activity (24-h urine norepinephrine) over 5 wk compared with their unstressed DR controls. Terminally, there was a 35% increase in the paraventricular nucleus corticotropin-releasing hormone mRNA expression. On the other hand, stressed DIO rats showed only a transient early increase in open-field activity and a terminal increase in basal corticosterone levels as the only effects of stress. Thus DIO rats are hyporesponsive to chronic stress compared with DR rats. This is in keeping with several other known differences in hypothalamopituitary and autonomic function in this model.

Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas

Abstract: Siotone (ST) is a herbal formulation comprising of Withania somnifera, Ocimum sanctum, Asparagus racemosus, Tribulus terristris and shilajit, all of which are classified in Ayurveda as rasayanas which are reputed to promote physical and mental health, improve defence mechanisms of the body and enhance longevity. These attributes are similar to the modern concept of adaptogenic agents, which are, known to afford protection of the human physiological system against diverse stressors. The present study was undertaken to investigate the adaptogenic activity of ST against chronic unpredictable, but mild, footshock stress induced perturbations in behaviour (depression), glucose metabolism, suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in CF strain albino rats. Gastric ulceration, adrenal gland and spleen weights, ascorbic acid and corticosterone concentrations of adrenal cortex, and plasma corticosterone levels, were used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. Additionally, rat brain levels of tribulin, an endogenous endocoid postulated to be involved in stress, were also assessed in terms of endogenous monoamine oxidase (MAO) A and MAOB inhibitory activity. Chronic unpredictable footshock induced marked gastric ulceration, significant increase in adrenal gland weight and plasma corticosterone levels, with concomitant decreases in spleen weight, and concentrations of adrenal gland ascorbic acid and corticosterone. These effects were attenuated by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.), administered once daily over a period of 14 days, the period of stress induction. Chronic stress also induced glucose intolerance, suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests), and immunosuppression (leucocyte migration inhibition and sheep RBC challenged increase in paw oedema in sensitized rats). All these chronic stress-induced perturbations were attenuated, dose-dependently by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.). Chronic stress-induced increase in rat brain tribulin activity was also reversed by these doses of ST and by PG. The results indicate that ST has significant adaptogenic activity, qualitatively comparable to PG, against a variety of behavioural, biochemical and physiological perturbations induced by unpredictable stress, which has been proposed to be a better indicator of clinical stress than acute stress parameters. The likely contribution of the individual constituents of ST in the observed adaptogenic action of the polyherbal formulation, have been discussed.