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Restraint Stress (restraint + stress)
Kinds of Restraint Stress Selected AbstractsEffects of neonatal novelty exposure on sexual behavior, fear, and stress-response in adult ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2007Fernando Benetti Abstract Environmental stimuli in early life may result in permanent behavioral and physiological changes. Present study evaluated the effects of exposing pups to a novel environment on behaviors (open-field test and sexual behavior) and prolactin stress-responses in adult male rats. Half of a litter was daily removed outside (OUT) from the nest and stimulated by handling for 3 min, while the other half remained inside (IN) the nest and was also handled for the same period during the first 10 days postpartum. Maternal behavior after all the pups were returned to the nest was not different between IN and OUT littermates. In adulthood, OUT males showed increased general and central locomotion activity in the open-field test, reduced sexual behavior, and attenuated prolactin secretion in response to restraint stress compared with the IN littermates. The repeated exposition of rat pups to a novel environment is a causal factor for the long-lasting behavioral and endocrine changes. The premature exposition of the pup to unfamiliar environments decreases fear and stress-response, and also reduces sexual behavior. We suggest that the absence of the odor of the mother may be crucial to explain the effects detected in adulthood. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 258,264, 2007. [source] Prenatal restraint stress differentially modifies basal and stimulated dopamine and noradrenaline release in the nucleus accumbens shell: an ,in vivo' microdialysis study in adolescent and young adult ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Alessandra Silvagni Abstract Gestational stress [prenatal stress (PNS)] has been associated with low birth weight, preterm delivery, and higher vulnerability to psychiatric disorders such as schizophrenia, depression or attention deficit with hyperactivity disorder. The alteration of catecholamine transmission has been attributed a major role in the etiology of psychiatric disturbances. We investigated the effect of PNS on basal and stimulated dopamine and noradrenaline output in the nucleus accumbens of freely moving adolescent and young adult rats (30,35 and 60,70 postnatal days respectively) because of the importance of this area in drug dependence and possibly in psychiatric disorders that are treated with drugs that act on dopamine and noradrenaline transmission. Stimulation was obtained with intraperitoneal amphetamine (0.25 mg/kg) or subcutaneous nicotine (0.4 mg/kg). The results showed the following: (i) basal and amphetamine-stimulated dopamine output in adolescent and adult PNS rats is higher than in controls; (ii) nicotine-stimulated dopamine output is lower than in controls in adolescent but not in adult PNS rats; (iii) basal noradrenaline output is lower than in controls in adolescent but not in adult PNS rats; (iv) amphetamine-stimulated noradrenaline output is higher than in controls in adult but not in adolescent PNS rats; (v) nicotine-stimulated noradrenaline output in PNS rats is higher than in controls, although only in adults. These results show that PNS may produce a complex change in accumbal dopamine and noradrenaline transmission. We discuss the possibility that these changes might be correlated with the development of psychiatric disorders or with an increased vulnerability to drug addiction. [source] Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2008Meng-Yang Zhu Abstract Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with ,-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. [source] Individual differences in the effects of chronic prazosin hydrochloride treatment on hippocampal mineralocorticoid and glucocorticoid receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Mohamed Kabbaj Abstract The aim of this study was to investigate the noradrenergic regulation of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in high responder (HR) and low responder (LR) male rats, an animal model of individual differences in hypothalamo-pituitary-adrenal axis activity and vulnerability to drugs of abuse. The effects of a chronic treatment with the noradrenergic ,1 antagonist (1-[4-amino-6,7-dimethoxy-2-quinazolinyl]-4-[2-furanylcarbonyl] piperazine) hydrochloride (prazosin) (0.5 mg/kg, i.p., 35 days) were assessed on stress-induced corticosterone (CORT) secretion and on hippocampal MRs and GRs in adrenally intact rats. In order to ascertain whether the effects of chronic prazosin treatment on hippocampal MRs and GRs were direct or indirect, through prazosin-induced CORT secretion, we also assessed the effects of the same treatment on adrenalectomized rats with CORT substitutive therapy. When compared with LR rats, HR rats exhibited a delayed return to the basal level of CORT following acute restraint stress; this was associated with a lower binding of MRs and GRs in HR rats than in LR rats. Chronic prazosin treatment had no effect in HR animals but markedly reduced hippocampal MRs and GRs, and increased stress-induced CORT secretion in LR rats. In LR adrenalectomized rats, prazosin reduced hipppocampal MRs but did not change GRs. Our results provide evidence of a differential regulation by noradrenaline of hippocampal MRs and GRs in HR and LR rats. These data could have clinical implications in terms of individual differences in the resistance to antidepressant treatments and individual differences in drug abuse. [source] Rapid reversal of stress induced loss of synapses in CA3 of rat hippocampus following water maze trainingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003Carmen Sandi Abstract The impact was examined of exposing rats to two life experiences of a very different nature (stress and learning) on synaptic structures in hippocampal area CA3. Rats were subjected to either (i) chronic restraint stress for 21 days, and/or (ii) spatial training in a Morris water maze. At the behavioural level, restraint stress induced an impairment of acquisition of the spatial response. Moreover, restraint stress and water maze training had contrasting impacts on CA3 synaptic morphometry. Chronic stress induced a loss of simple asymmetric synapses [those with an unperforated postsynaptic density (PSD)], whilst water maze learning reversed this effect, promoting a rapid recovery of stress-induced synaptic loss within 2,3 days following stress. In addition, in unstressed animals a correlation was found between learning efficiency and the density of synapses with an unperforated PSD: the better the performance in the water maze, the lower the synaptic density. Water maze training increased the number of perforated synapses (those with a segmented PSD) in CA3, both in stressed and, more notably, in unstressed rats. The distinct effects of stress and learning on CA3 synapses reported here provide a neuroanatomical basis for the reported divergent effects of these experiences on hippocampal synaptic activity, i.e. stress as a suppressor and learning as a promoter of synaptic plasticity. [source] Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Kara Pham Abstract Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural cell adhesion molecule, whereas 3 weeks of chronic restraint stress suppressed proliferation by 24% and increased polysialylated neural cell adhesion molecule expression by 40%. The study was extended for an additional 3 weeks to trace the survival and development of the cells born after the initial 3 weeks of restraint. Rats subjected to 6 weeks of daily restraint stress exhibited suppressed cell proliferation and attenuated survival of the recently born cells after the extended time course, resulting in a 47% reduction of granule cell neurogenesis. Furthermore, 6 weeks of chronic stress significantly reduced the total number of granule cells by 13% and the granule cell layer volume by 5%. Expression of polysialylated neural cell adhesion molecule followed a biphasic time course, displaying a significant up-regulation after 3 weeks of daily restraint stress that was lost after 6 weeks of stress. These studies may help us understand the basis for hippocampal shrinkage and raise questions about the ultimate reversibility of the effects of chronic stress. [source] Decreased glucocorticoid receptor mRNA and dysfunction of HPA axis in rats after removal of the cholinergic innervation to hippocampus.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2002Jung-Soo Han Abstract Excess exposure to glucocorticoids can have deleterious effects on physiology and cognition. Glucocorticoids acting via receptors located in hippocampal neurons contribute to negative feedback after stress by terminating the further release of glucocorticoids. The current study investigated the effects of selective immunolesions of septo-hippocampal cholinergic neurons on hippocampal corticosterone receptor mRNA and on hypothalamic-pituitary-adrenal (HPA) activity. As evaluated by in situ hybridization, hippocampal glucocorticoid receptor (GR) mRNA, but not mineralocorticoid receptor (MR) mRNA, was significantly decreased in lesioned rats compared to controls. In a companion study, the peak corticosterone response to one hour of restraint stress did not differ between lesion and control groups but the post-stress decline of corticosterone was more protracted in the lesioned rats. These findings are discussed in terms of their possible relevance to ageing as age-related degeneration of the basal forebrain cholinergic system may contribute to the commonly observed dysfunction of the HPA axis in older animals. [source] Postnatal handling reverses social anxiety in serotonin receptor 1A knockout miceGENES, BRAIN AND BEHAVIOR, Issue 1 2010C. Zanettini Mice lacking the serotonin receptor 1A (Htr1a knockout, Htr1aKO) show increased innate and conditioned anxiety. This phenotype depends on functional receptor activity during the third through fifth weeks of life and thus appears to be the result of long-term changes in brain function as a consequence of an early deficit in serotonin signaling. To evaluate whether this phenotype can be influenced by early environmental factors, we subjected Htr1a knockout mice to postnatal handling, a procedure known to reduce anxiety-like behavior and stress responses in adulthood. Offspring of heterozygous Htr1a knockout mice were separated from their mother and exposed 15 min each day from postnatal day 1 (PD1) to PD14 to clean bedding. Control animals were left undisturbed. Maternal behavior was observed during the first 13 days of life. Adult male offspring were tested in the open field, social approach and resident,intruder tests and assessed for corticosterone response to restraint stress. Knockout mice showed increased anxiety in the open field and in the social approach test as well as an enhanced corticosterone response to stress. However, while no effect of postnatal handling was seen in wild-type mice, handling reduced anxiety-like behavior in the social interaction test and the corticosterone response to stress in knockout mice. These findings extend the anxiety phenotype of Htr1aKO mice to include social anxiety and demonstrate that this phenotype can be moderated by early environmental factors. [source] Stress differentially regulates the effects of voluntary exercise on cell proliferation in the dentate gyrus of miceHIPPOCAMPUS, Issue 10 2009Timal S. Kannangara Abstract It has been well-established that cell proliferation and neurogenesis in the adult mouse dentate gyrus (DG) can be regulated by voluntary exercise. Recent evidence has suggested that the effects of voluntary exercise can in turn be influenced by environmental factors that regulate the amount of stress an animal is exposed to. In this study, we use bromodeoxyuridine and proliferating cell nuclear antigen immunohistochemistry to show that voluntary exercise produces a significant increase in cell proliferation in the adult mouse DG in both isolated and socially housed mice. This effect on proliferation translates into an increase in neurogenesis and neuronal branching of new neurons in the mice that exercised. Although social condition did not regulate proliferation in young adult mice, an effect of social housing could be observed in mice exposed to acute restraint stress. Surprisingly, only exercising mice housed in isolated conditions showed an increase in cellular proliferation following restraint stress, whereas socially housed, exercising mice, failed to show a significant increase in proliferation. These findings indicate that social housing may increase the effects of any stressful episodes on hippocampal neurogenesis in the mouse DG. © 2008 Wiley-Liss, Inc. [source] The effects of exercise and stress on the survival and maturation of adult-generated granule cells,HIPPOCAMPUS, Issue 10 2009Jason S. Snyder Abstract Stress strongly inhibits proliferation of granule cell precursors in the adult dentate gyrus, whereas voluntary running has the opposite effect. Few studies, however, have examined the possible effects of these environmental manipulations on the maturation and survival of young granule cells. We examined the number of surviving granule cells and the proportion of young neurons that were functionally mature, as defined by seizure-induced immediate-early gene (IEG) expression, in 14- and 21-day-old granule cells in mice that were given access to a running wheel, restrained daily for 2 h, or given no treatment during this period. Treatments began 2 days after BrdU injection, to isolate effects on survival from those on cell proliferation. We found a large increase in granule cell survival in running mice when compared with controls at both time points. In addition, running increased the proportion of granule cells expressing the IEG Arc in response to seizures, suggesting that it speeds incorporation into circuits, i.e., functional maturation. Stressed mice showed no change in Arc expression, compared with control animals, but, surprisingly, showed a transient increase in survival of 14-day-old granule cells, which was gone 7 days later. Examination of cell proliferation, using the endogenous mitotic marker PCNA showed an increase in cell proliferation after 12 days of running but not after 19 days of running. The number of proliferating cells was unchanged 24 h after the 12th or 19th episode of daily restraint stress. These findings demonstrate that running has strong effects on survival and maturation of young granule cells as well as their birth and that stress can have positive but short-lived effects on granule cell survival. Published 2009 Wiley-Liss, Inc. [source] Fetal and offspring arrhythmia following exposure to nicotine during pregnancyJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2010Yu Feng Abstract Although recent studies have demonstrated prenatal nicotine can increase cardiovascular risk in the offspring, it is unknown whether exposure to nicotine during pregnancy also may be a risk for development of arrhythmia in the offspring. In addition, in previous studies of fetal arrhythmia affected by smoking, only two patterns, bradycardia and tachycardia, were observed. The present study examined acute effects of maternal nicotine on the fetal arrhythmia in utero, and chronic influence on offspring arrhythmia at adult stage following prenatal exposure to nicotine. Nicotine was administered to pregnant ewes and rats. In the fetal sheep, intravenous nicotine not only induced changes of fetal heart rate, but also caused cardiac cycle irregularity, single and multiple dropped cardiac cycles. Although maternal nicotine had no influence on fetal blood pH, lactic acid, hemocrit, Na+, K+ levels and plasma osmolality, fetal blood PO2 levels were significantly decreased following maternal nicotine in ewes. In offspring rats at 4,5 months after birth, prenatal exposure to nicotine significantly increased heart rate and premature ventricular contraction in restraint stress. In addition, arrhythmias induced by injection of nicotine were higher in the offspring prenatal exposure to nicotine in utero. The results provide new evidence that exposure to nicotine in pregnancy can cause fetal arrhythmia in various patterns besides tachycardia and bradycardia, the possible mechanisms for nicotine-induced fetal arrhythmia included in utero hypoxia. Importantly, following exposure to nicotine significantly increased risk of arrhythmia in the adult offspring. The finding offers new insight for development of cardiac rhythm problems in fetal origins. Copyright © 2009 John Wiley & Sons, Ltd. [source] Circadian and age-related changes in stress responsiveness of the adrenal cortex and erythrocyte antioxidant enzymes in female rhesus monkeysJOURNAL OF MEDICAL PRIMATOLOGY, Issue 5 2008Nadezhda D. Goncharova Abstract Background, The objective of this study was to evaluate the role of the adrenal cortex in the regulation of antioxidant enzyme defense and to characterize this regulation in different age periods. Methods, Five young and five old female rhesus monkeys were subjected to 2 hours squeeze cage restraint stress at 0900 or 1500 hours. Plasma levels of corticosteroids and activities of erythrocyte antioxidant enzymes were measured before the stress and 30, 60, 120, 240 minutes after beginning of the stress. Results, Young monkeys showed a circadian rhythm in stress responsiveness as measured by corticosteroids and glutathione reductase. The rhythm was attenuated in old animals. Age-related changes in the overall level of response to the afternoon stress were also seen in the corticosteroid and glutathione reductase measures. Conclusions, The study demonstrated that corticosteroids play an essential role in the regulation of antioxidant enzyme defense in stress conditions and that the reliability of their regulation decreases with age. [source] Stress Response of Prolactin-Releasing Peptide Knockout Mice as to Glucocorticoid SecretionJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2010A. Mochiduki Prolactin-releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin-releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP-KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion. [source] The Medial Amygdala Modulates Body Weight but not Neuroendocrine Responses to Chronic StressJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2010M. B. Solomon Stress pathologies such as depression and eating disorders (i.e. anorexia nervosa) are associated with amygdalar dysfunction, which are linked with hypothalamic-pituitary-adrenal axis (HPA) axis hyperactivity. The medial amygdaloid nucleus (MeA), a key output nucleus of the amygdaloid complex, promotes HPA axis activation to acute psychogenic stress and is in a prime position to mediate the deleterious effects of chronic stress on physiology and behaviour. The present study tests the hypothesis that the MeA is necessary for the development of maladaptive physiological changes caused by prolonged stress exposure. Male rats received bilateral ibotenate or sham lesions targeting the MeA and one half underwent 2 weeks of chronic variable stress (CVS) or served as home cage controls. Sixteen hours post CVS, all animals were exposed to an acute restraint challenge. CVS induced thymic involution, adrenal hypertrophy, and attenuated body weight gain and up-regulation of hypothalamic corticotrophin-releasing hormone mRNA expression. Consistent with previous literature, lesions of the MeA dampened stress-induced increases in corticosterone after 30 min of exposure to acute restraint stress. However, this effect was independent of CVS exposure, suggesting that the MeA may not be critical for modulating neuroendocrine responses after chronic HPA axis drive. Interestingly, lesion of the MeA modestly exaggerated the stress-induced attenuation of weight gain. Overall, the data obtained suggest that the MeA modulates the neuroendocrine responses to acute but not chronic stress. In addition, the data suggest that the MeA may be an important neural component for the control of body weight in the face of chronic stress. [source] Glucocorticoids and the Development of Agonistic Behaviour during Puberty in Male Golden HamstersJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2005J. C. Wommack Abstract During puberty, the agonistic behaviour of male golden hamsters undergoes a transition from play fighting to adult aggression. Repeated exposure to social stress early in puberty accelerates this transition. The present study investigated the possible role of glucocorticoids on the maturation of agonistic behaviour. First, we compared serum cortisol levels following a 20-min restraint stress during early puberty, mid-puberty or adulthood. Across puberty, animals exhibited a two-fold increase in post-restraint cortisol levels. We also compared corticotrophin-releasing hormone (CRH) immunoreactive fibres projecting to the median eminence between animals in early puberty and adulthood. The CRH fibre density was two-fold greater in adults compared to juveniles. Furthermore, we investigated the effects of stress hormones on the maturation of agonistic behaviour. Male hamsters were injected daily with dexamethasone, a corticosteroid receptor type II agonist (0, 10 or 40 µg/100 g), early in puberty from postnatal day 31 (P-31) to P-36. When paired with a smaller and younger intruder on P-37, attack frequency did not differ between groups. However, dexamethasone-treated animals showed a dose-dependent decrease in the percentage of play-fighting attacks and an increase in the percentage of adult attacks. In summary, puberty can be described as a period of increasing hypothalamic-pituitary-adrenal activity in male golden hamsters. Moreover, increasing glucocorticoid levels influence the maturation of agonistic behaviour. These data shed new light on the neuroendocrine mechanisms that regulate the maturation of social behaviours during puberty. [source] APJ Receptor mRNA Expression in the Rat Hypothalamic Paraventricular Nucleus: Regulation By Stress and GlucocorticoidsJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2003A.-M. O'Carroll Abstract The apelin receptor (APJ receptor, APJR) has recently come to prominence following the isolation and identification of its endogenous ligand, apelin, from bovine stomach tissue extracts. Investigation of APJR mRNA expression has revealed a hypothalamic distribution similar to that of vasopressin suggesting that the apelin,APJR system may be involved in the regulation of the hypothalamic-adrenal-pituitary (HPA) stress axis. To investigate whether APJR is involved in the regulation of hypothalamic function during stress, APJR mRNA expression levels were measured by in situ hybridization in the hypothalamus of rats subjected to acute and repeated restraint stress. Acute stress caused an increase in APJR mRNA expression in the hypothalamic parvocellular paraventricular nucleus (pPVN) while repeated restraint stress induced a sustained up-regulation of pPVN APJR mRNA expression in intact rats. Removal of endogenous glucocorticoids by adrenalectomy also resulted in an increased expression of APJR mRNA in the PVN, suggesting a negative regulation of APJR mRNA expression by glucocorticoids. The role of glucocorticoids in mediating these stress-induced changes was investigated by analysing the effects of acute and repeated restraint stress on APJR mRNA levels in adrenalectomized rats. In these rats, APJR mRNA expression levels did not change above the already elevated levels of adrenalectomized-control rats. These data suggest that acute and repeated stress exert a stimulatory influence on APJR mRNA expression at the hypothalamic level that may be dependent on basal levels of circulating glucocorticoids, and further suggest a role for APJR in the regulation of hypothalamic function. [source] Habituation and Cross-Sensitization of Stress-Induced Hypothalamic-Pituitary-Adrenal Activity: Effect of Lesions in the Paraventricular Nucleus of the Thalamus or Bed Nuclei of the Stria TerminalisJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2002G. A. Fernandes Abstract Habituation of the hypothalamic-pituitary-adrenal (HPA) response to chronic intermittent restraint stress (30 min/day for 15 days) and the cross-sensitization to a heterotypic stress [i.p. lipopolysaccharide (LPS)] were investigated in intact male Sprague Dawley rats, and in rats bearing quinolinic acid lesions to the medial anterior bed nuclei of the stria terminalis (BST) or anterior region of the paraventricular nucleus of the thalamus (PVT). In intact animals, a single period of restraint increased plasma corticosterone levels at 30 min and led to an increase in corticotropin-releasing hormone (CRH) mRNA levels in the PVN at 3 h. LPS had a smaller effect on corticosterone and more variable effect on CRH mRNA. Chronic intermittent restraint stress caused a decrease in body weight and increase in adrenal weights, with concomitant increase in basal corticosterone levels. These animals also displayed marked habituation of the corticosterone and CRH mRNA responses to the homotypic stress of restraint, but no loss of the corticosterone response to the heterotypic stress of LPS and a cross-sensitization of the CRH mRNA response. This pattern of stress responses in control and chronically stressed animals was not significantly affected by lesions to the PVT or BST, two areas which have been implicated in the coping response to stress. Thus, these data provide evidence for independent adaptive mechanisms regulating HPA responses to psychological and immune stressors, but suggest that neither the medial anterior BST nor the anterior PVT participate in the mechanisms of habituation or cross-sensitization. [source] Blunted Pituitary-Adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone TreatmentJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2000K. Felszeghy Abstract Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 µg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 µg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma cncentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. [source] Conserved cellular function and stress-mediated regulation among members of the proteolipid protein familyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2010Marķa E. Fernįndez Abstract Chronic stress causes morphological alterations in the hippocampus of rodents and tree shrews, including atrophy of CA3 dendrites and loss of synapses. The molecular mechanisms underlying these structural changes remain largely unknown. We have previously identified M6a as a stress responsive gene and shown that M6a is involved in filopodium/spine outgrowth and, likely, synapse formation. M6a belongs to the proteolipid protein (PLP) family, all of their members having four transmembrane domains that allow their localization at the plasma membrane. In the present work, we analyzed other members of this family, the closely related M6b as well as PLP and its splice variant DM20. We found that chronic restraint stress in mice reduces M6b and DM20, but not PLP, mRNA levels in the hippocampus. In addition, M6b and DM20, but again not PLP, induce filopodium formation in primary cultures of hippocampal neurons. Several M6b protein isoforms were studied, all of them having similar effects except for the one lacking the transmembrane domains. Our results reveal a conserved cellular function and a stress-mediated regulation among members of the proteolipid protein family, suggesting an involvement of proteolipid proteins in the stress response. © 2009 Wiley-Liss, Inc. [source] Regulation of relaxin 3 gene expression via cAMP-PKA in a neuroblastoma cell lineJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2009Masaki Tanaka Abstract Relaxin 3 is expressed in neurons of the brain stem that inneravate wide areas of the forebrain. Relaxin 3 mRNA levels in these neurons are increased in response to restraint stress, and by central administration of corticotropin-releasing factor (CRF). In the present study, we observed that relaxin 3 was expressed in a mouse neuroblastoma cell line, Neuro2a, and investigated the intracellular signaling that activated relaxin 3 gene transcription in vitro. By means of a clone stably transfected with a relaxin 3 promoter-EGFP gene, we observed that dibutyryl cyclic AMP and forskolin increased the relaxin 3 promoter activity. These increases were inhibited by pretreatment with PKA inhibitors, H89 and KT5720. Moreover, the promoter activity was enhanced by CRF treatment after expression of CRF-R1 receptor on the cells. Taken together, these results indicate that relaxin 3 transcription is activated via the cAMP-PKA pathway in the downstream of CRF-R1. © 2008 Wiley-Liss, Inc. [source] Roles of nocturnal melatonin and the pineal gland in modulation of water-immersion restraint stress-induced gastric mucosal lesions in ratsJOURNAL OF PINEAL RESEARCH, Issue 2 2001Migusa Otsuka The roles of melatonin and the pineal gland in the circadian variation of water-immersion restraint stress-induced gastric mucosal lesions in rats were investigated. Fasted rats were subjected to water-immersion restraint stress during both the diurnal and nocturnal phases of a light:dark cycle. Pinealectomized and sham-operated rats were also subjected to water-immersion restraint stress at night. The lesion area after 4 hr of stress during the dark phase was significantly lower than in light-phase controls. Pinealectomy increased the lesion area in the dark phase, compared to the sham operation, but this effect was counteracted by intracisternal melatonin preadministration at a dose of 100 ng/rat. Melatonin concentrations in control rats during the light phase were significantly increased 4 hr after water-immersion restraint stress. In contrast, melatonin concentrations 4 hr after water-immersion restraint stress in the dark phase were significantly depressed compared with the control levels at the corresponding time. Melatonin levels after stress exposure were markedly decreased in pinealectomized rats as compared with sham-operated rats. These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats and that melatonin responses to water-immersion restraint stress differ between day and night. The pineal gland modulates the stress response and melatonin contributes to gastric protection via a mechanism involving the central nervous system. [source] Ethanol Attenuates Spatial Memory Deficits and Increases mGlu1a Receptor Expression in the Hippocampus of Rats Exposed to Prenatal StressALCOHOLISM, Issue 8 2009Vincent Van Waes Background:, Although it is generally believed that chronic ethanol consumption impairs learning and memory, results obtained in experimental animals are not univocal, and there are conditions in which ethanol paradoxically improves cognitive functions. In the present work, we investigated the effects of prenatal stress and of chronic ethanol exposure during adulthood on spatial memory in rats. Methods:, Rats were subjected to a prenatal stress delivered as 3 daily 45-minute sections of restraint stress to the mothers during the last 10 days of pregnancy (PRS rats). After 7 months of ethanol exposure (ethanol 10%, oral intake), memory performances were evaluated in a spatial discrimination test in control and PRS male rats. Then, the oxidative damages and the expression of metabotropic glutamate (mGlu) receptors were assessed in their hippocampus. Results:, Chronic ethanol exposure resulted in a reduced performance in a spatial recognition task in control animals. Unexpectedly, however, the same treatment attenuated spatial memory deficits in rats that had been subjected to prenatal stress. This paradigm of ethanol administration did not produce detectable signs of oxidative damage in the hippocampus in either unstressed or PRS rats. Interestingly, ethanol intake resulted in differential effects in the expression of mGlu receptor subtypes implicated in mechanisms of learning and memory. In control rats, ethanol intake reduced mGlu2/3 and mGlu5 receptor levels in the hippocampus; in PRS rats, which exhibited a constitutive reduction in the levels of these mGlu receptor subtypes, ethanol increased the expression of mGlu1a receptors but did not change the expression of mGlu2/3 or mGlu5 receptors. Conclusion:, Our findings support the idea that stress-related events occurring before birth have long-lasting effects on brain function and behavior, and suggest that the impact of ethanol on cognition is not only dose- and duration-dependent, but also critically influenced by early life experiences. [source] Gender and Age at Drinking Onset Affect Voluntary Alcohol Consumption but Neither the Alcohol Deprivation Effect nor the Response to Stress in MiceALCOHOLISM, Issue 12 2008Sophie Tambour Background:, Epidemiological studies suggest that initiation of alcohol drinking at an early age is associated with an increased risk of developing an alcohol use disorder later in life. Nevertheless, relatively few studies using animal models have investigated the relationship between age of onset of drinking and ethanol drinking patterns in adulthood. Besides age at drinking onset, other factors such as gender could also affect the pattern of development of alcohol consumption. In rodents, many studies have shown that females drink more than males. However, even if it is assumed that hormonal changes occurring at puberty could explain these differences, only one study performed in rats has investigated the emergence of sex-specific alcohol drinking patterns in adolescence and the transition from adolescence to adulthood. The aim of the present study was to compare the acquisition of voluntary alcohol consumption, relapse-like drinking (the Alcohol Deprivation Effect,ADE) and stress-induced alcohol drinking in male and female outbred mice that acquired alcohol consumption during adolescence or adulthood. Methods:, Separate groups of naļve female and male WSC-1 mice aged ± 28 days (adolescents) or ±70 days (adults) were given ad libitum access to water and 6% ethanol solution for 8 weeks (1st to 8th week) before undergoing a 2-week deprivation phase (9th and 10th week). After the deprivation period, 2-bottle preference testing (ethanol vs. water) resumed for 3 weeks (11th to 13th). During the 13th week, all animals were subjected to restraint stress for 2 consecutive days. Results:, Over the entire time course of the experiment, ethanol intake and preference increased in females (both adults and adolescents). Adolescent animals (both females and males) showed a transient increase in alcohol consumption and preference compared to adults. However, by the end of continuous alcohol exposure (when all mice were adults), ethanol intake was not affected by age at drinking onset. A deprivation phase was followed by a rise in ethanol intake (ADE) that was not affected by sex or age. Finally, stress did not alter alcohol self-administration either during or after its occurrence. Conclusions:, Emergence of greater alcohol consumption in adult females does not seem to be limited to a specific developmental period (i.e., puberty). Age of voluntary drinking onset (adolescence vs. adulthood) does not affect eventual alcohol intake in adult WSC-1 mice and does not modify the transient increase in ethanol consumption after alcohol deprivation. [source] Remission and Resurgence of Anxiety-Like Behavior Across Protracted Withdrawal Stages in Ethanol-Dependent RatsALCOHOLISM, Issue 9 2007Yu Zhao Background:, Alcohol dependence is a chronic disorder in which withdrawal symptoms often persist after detoxification. The purpose of the present experiment was to characterize susceptibility to stress and anxiogenic stimuli in rats over an extended time period following ethanol withdrawal. Methods:, Male Wistar rats were made dependent via ethanol vapor exposure. The rats were then tested in the elevated plus-maze during acute ethanol withdrawal (ACW, ,8 hour), early "protracted" withdrawal (EPW, 2 weeks), or late "protracted" withdrawal (LPW, 6, 12 weeks) following brief restraint or no stress. Principal components analysis was used to identify constructs underlying plus-maze behavior. Results:, Three factors characterized plus-maze performance: anxiety, locomotor activity, and risk assessment/decision making. Spontaneous anxiety-like behavior was increased during ACW, decreased to levels of ethanol-naļve controls during EPW, but markedly resurged during LPW. Withdrawal did not alter sensitivity to the anxiety-like effects of restraint stress. All ethanol-dependent rats showed locomotor hypoactivity that, in contrast to anxiety, remained stable throughout all withdrawal stages. Neither ethanol withdrawal nor restraint stress altered mean "risk assessment/decision making" scores, though ethanol withdrawal altered the emission of "risk assessment/decision making" behavior in relation to anxiety-like behavior and behavioral activation state. Conclusions:, The findings illustrate and model the spontaneous, severe, and long-lasting nature of behavioral abnormalities that accompany withdrawal from chronic, intermittent ethanol intoxication. The dynamic remission and resurgence in symptoms of negative affect (i.e., behavioral signs of anxiety) during "protracted" withdrawal may complicate recovery from alcoholism. [source] Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral painNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2010H. Eutamene Abstract Background, Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS-C. Therefore, we investigated the anti-nociceptive properties of linaclotide in rodent models of inflammatory and non-inflammatory visceral pain and determined whether these pharmacological effects are linked to the activation of guanylate cyclase C (GC-C). Methods,Orally administered linaclotide was evaluated in non-inflammatory acute partial restraint stress (PRS) and acute water avoidance stress (WAS) models in Wistar rats, and in a trinitrobenzene sulfonic acid (TNBS)-induced inflammatory model in Wistar rats and GC-C null mice. Key Results,In TNBS-induced colonic allodynia, linaclotide significantly decreased the number of abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity change in response to distending pressures after TNBS. However, linaclotide had no effect on visceral sensitivity under basal conditions. In addition, linaclotide significantly decreased colonic hypersensitivity in the PRS and WAS models. In wild type (wt) and GC-C null mice, the instillation of TNBS induced similar hyperalgesia and allodynia. However, in post-inflammatory conditions linaclotide significantly reduced hypersensitivity only in wt mice, but not in GC-C null mice. Conclusions & Inferences,These findings indicate that linaclotide has potent anti-nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC-C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS-C. [source] Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in ratsNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2008K. Seto Abstract, Acotiamide hydrochloride (Z-338) is a member of new class prokinetic agents currently being developed for the treatment of functional dyspepsia (FD). DNA microarray analysis showed that acotiamide altered the expressions of stress-related genes such as , -aminobutyric acid (GABA) receptors, GABA transporters and neuromedin U (NmU) in the medulla oblongata or hypothalamus after administration of acotiamide. Therefore, effects of acotiamide on stress-related symptoms, delayed gastric emptying and feeding inhibition, in rats were examined. Acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both basal gastric emptying and feeding in intact rats, indicating that acotiamide exerted effects only on gastric emptying and feeding impaired by the stress. On the other hand, mosapride showed significant acceleration of gastric emptying in intact and restraint stress-induced model, and itopride showed no effect on restraint stress-induced delayed gastric emptying. In addition, gene expression of NmU increased by restraint stress was suppressed by administration of acotiamide, while acotiamide had no effect on delayed gastric emptying induced by an intracerebroventricular administration of NmU, suggesting that the suppressive effect of acotiamide on gene expression of NmU might be important to restore delayed gastric emptying or feeding inhibition induced by restraint stress. These findings suggest that acotiamide might play an important role in regulation of stress response. As stress is considered to be a major contributing factor in the development of FD, the observed effects may be relevant for symptom improvement in FD. [source] Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of actionNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2003J. Fioramonti Abstract The involvement of neurokinin receptors in visceral nociception is well documented. However, the role and localization of NK3 receptors is not clearly established. This study was designed to determine whether NK3 receptor antagonists crossing (talnetant) or not (SB-235375) the blood,brain barrier reduce the nociceptive response to colo-rectal distension (CRD) and whether NK3 antagonism reduces inflammation- or stress-induced hypersensitivity to rectal distension. Isobaric CRD and isovolumic rectal distensions were performed in rats equipped with intramuscular electrodes to record abdominal muscle contractions. In controls, CRD induced a pressure-related (15,60 mmHg) increase in the number of abdominal contractions. Both talnetant and SB-235375 [50 mg kg,1, per oral (p.o.)], which had no effect on colo-rectal tone, reduced the number of contractions associated with CRDs from 30 to 60 mmHg. Three days after rectal instillation of TNBS, abdominal contractions were increased for rectal distension volume of 0.4 mL. This effect was not modified by talnetant (30 mg kg,1, p.o.). Partial restraint stress increased abdominal contractions at all distension volumes (0,1.2 mL). Talnetant (10 mg kg,1, p.o.) abolished the increase observed for 0.8 and 1.2 mL. These results indicate that peripheral NK3 receptor antagonism reduced nociception associated with CRD and hypersensitivity induced by stress but not inflammation. [source] Antiulcerogenic activity of crude ethanol extract and some fractions obtained from aerial parts of Artemisia annua L.PHYTOTHERAPY RESEARCH, Issue 8 2001Patrķcia Corrźa Dias Abstract The resulting enriched sesquiterpene lactone fraction and the crude ethanol extract of Artemisia annua L. aerial parts, showed antiulcerogenic activity when administered orally, on the indomethacin induced ulcer in rats. The sesquiterpene lactone fraction yielded three different polarity fractions on column chromatography as follows: non-polar, medium polarity and polar fraction, When submitted to the same indomethacin-induced ulcer in rats they resulted in different levels of inhibition of the ulcerative lesion index. The participation of nitric oxide was evaluated on an ethanol-induced ulcer model which had a previous administration of L -NAME, a NO-synthase inhibitor. Under these conditions, the medium polarity fraction maintained the antiulcerogenic activity, suggesting that nitric oxide could not be involved in the antiulcerogenic activity. When the animal groups were treated with N-ethylmaleimide, an alkylator of sulphhydryl groups, using the same experimental model, the medium polarity fraction maintained its antiulcerogenic activity, suggesting that the pharmacological mechanism is not related to non-protein sulphydryl compounds. On the ethanol-induced ulcer with previous indomethacin treatment, the medium polarity fraction lost its antiulcerogenic activity indicating that the active compounds of Artemisia annua L. increase the prostaglandin levels in the gastric mucosa. This hypothesis was reinforced by an increase of adherent mucus production by the gastric mucosa, produced by the medium polarity fraction on the hypothermic restraint stress induced ulcer model. Copyright © 2001 John Wiley & Sons, Ltd. [source] Acute stress enhances contact dermatitis by promoting nuclear factor-,B DNA-binding activity and interleukin-18 expression in miceTHE JOURNAL OF DERMATOLOGY, Issue 6 2010Jing ZHANG Abstract Psychological stress adversely affects the immune system, and aggravates various skin diseases, such as psoriasis, alopecia areata and atopic dermatitis. However, the precise underlying mechanisms remain to be elucidated. The goal of this study was to use a murine restraint stress model to determine the mechanisms by which psychological stress modulates immune response in contact dermatitis. In the present study, mice were sensitized and challenged on the skin with 2,4-dinitrofluorobenzene. Acute restraint stress was administrated to healthy or sensitized mice before challenge, and nuclear factor (NF)-,B DNA-binding activation of nuclear protein and expression of interleukin (IL)-18 mRNA in murine spleen lymphocytes was detected. Chemical sympathectomy was performed using the neurotoxin 6-hydroxy-dopamine to determine the effect of the sympathetic nervous system. The experiment showed that restraint stress induced a series of changes which include increasing of NF-,B DNA-binding activity and IL-18 mRNA expression in spleen lymphocytes and enhancement of contact hypersensitivity response, and these changes may be mediated by the sympathetic nervous system. These findings provide new insights into the roles of the nervous system in the aggravation of skin diseases. [source] Effect of thyroid hormones on stress ulcer formationANZ JOURNAL OF SURGERY, Issue 9 2002Ayhan Koyuncu Background: Stress ulcers are gastric mucosal lesions that may cause life-threatening upper gastrointestinal bleeding. Although it is known that hyperthyroid status prevents stress ulcer formation, the effect of thyroid hormones given just as the stress is beginning has not been studied. The aim of this study was to assess the effect of thyroid hormone supplementation on gastric stress ulcers at the beginning of the restraint stress. Methods: Thyroid hormones were administered to rats 2 days before or at the beginning of the restraint stress. The linear length of the gastric mucosal lesions, mucosal pH and thyroid hormone levels were measured and histopathological examinations were carried out. Results: It was found that both triiodothyronin and thyroxin reduce the length and depth of the stress ulcers (P < 0.001). Conclusion: Although the mechanisms by which the thyroid hormones act on stress ulcers are uncertain, current experimental studies suggest that thyroid hormones reduce the formation of stress ulcers in rats when given before or at the beginning of the stress. [source] | ||||||||||||||||