Showing papers on "Corticosterone published in 2006"
TL;DR: The findings strongly suggest that synergistic actions of glucocorticoids and emotional arousal-induced noradrenergic activation of the basolateral complex of the amygdala (BLA) constitute a neural mechanism by which glucoc Corticoidoids may selectively enhance memory consolidation for emotionally arousing experiences.
Abstract: Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of long-term memories for emotionally arousing experiences but not that for less arousing or neutral information. However, previous studies have not determined the basis of such arousal-induced selectivity. Here we report the finding that endogenous noradrenergic activation of the basolateral complex of the amygdala (BLA) induced by emotional arousal is essential in enabling glucocorticoid memory enhancement. Corticosterone administered immediately after object recognition training enhanced 24-h memory of naive male rats but not that of rats previously habituated to the training context in order to reduce novelty-induced emotional arousal. The β-adrenoceptor antagonist propranolol administered either systemically or into the BLA blocked the corticosterone-induced memory enhancement. Further, in habituated rats, corticosterone activated BLA neurons, as assessed by phosphorylated cAMP response element binding (pCREB) immunoreactivity levels, and enhanced memory only when norepinephrine release was stimulated by administration of the α2-adrenoceptor antagonist yohimbine. These findings strongly suggest that synergistic actions of glucocorticoids and emotional arousal-induced noradrenergic activation of the BLA constitute a neural mechanism by which glucocorticoids may selectively enhance memory consolidation for emotionally arousing experiences.
472 citations
TL;DR: Exogenous ACTH administration to dexamethasone-blocked rats demonstrated that CVS increased maximal plasma and adrenal corticosterone responses to ACTH without affecting sensitivity, and increased adrenal weight after CVS is due to hyperplasia and hypertrophy that occur in specific adrenal subregions and is associated with increased maximal cortic testosterone responses toACTH.
Abstract: The adrenal gland is an essential stress-responsive organ that is part of both the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullary system. Chronic stress exposure commonly incr...
427 citations
TL;DR: It is demonstrated that elevated levels of glucocorticoids are able to activate microglia in vivo and suggest that stress is able to induce a pro-inflammatory response within the central nervous system.
360 citations
TL;DR: It is demonstrated that rosiglitazone attenuates learning and memory deficits in Tg2576 mice and suggested that the effects of the drug on learning andMemory, brain IDE levels, and brain Abeta42 levels in the mice may be due to its glucocorticoid-lowering actions.
320 citations
TL;DR: Odor-shock conditioning produces either olfactory preference or aversion in preweanling rats, depending on the context, and over-riding maternal suppression of cortic testosterone through intra-amygdala corticosterone infusions permits fear conditioning and amygdala activation.
Abstract: Odor-shock conditioning produces either olfactory preference or aversion in preweanling (12–15 days old) rats, depending on the context. In the mother's absence, odor-shock conditioning produces amygdala activation and learned odor avoidance. With maternal presence, this same conditioning yields an odor preference without amygdala activation. Maternal presence acts through modulation of pup corticosterone and corticosterone's regulation of amygdala activity. Over-riding maternal suppression of corticosterone through intra-amygdala corticosterone infusions permits fear conditioning and amygdala activation.
316 citations
TL;DR: The results demonstrate that glucocorticoids increase depression-like behavior in rats in a dose-dependent manner and disrupt normal HPA axis function, supporting the hypothesis that high levels of cortisol contribute to the etiology of depressive symptomatology in humans.
308 citations
TL;DR: Hormonal and neural responses in prepubertal and adult male rats after exposure to acute or more chronic restraint stress indicate that experience-dependent plasticity of the hypothalamic-pituitary-adrenal neuroendocrine axis is significantly influenced by pubertal maturation.
Abstract: Both the magnitude and the duration of the hormonal stress response change dramatically during neonatal development and aging as well as with prior experience with a stressor. However, surprisingly little is known with regard to how pubertal maturation and experience with stress interact to affect hypothalamic-pituitary-adrenal axis responsiveness. Because adolescence is a period of neurodevelopmental vulnerabilities and opportunities that may be especially sensitive to stress, it is imperative to more fully understand these interactions. Thus, we examined hormonal and neural responses in prepubertal (28 d of age) and adult (77 d of age) male rats after exposure to acute (30 min) or more chronic (30 min/d for 7 d) restraint stress. We report here that after acute stress, prepubertal males exhibited a significantly prolonged hormonal stress response (e.g. ACTH and total and free corticosterone) compared with adults. In contrast, after chronic stress, prepubertal males exhibited a higher response immediately after the stressor, but a faster return to baseline, compared with adults. Additionally, we demonstrate that this differential stress reactivity is associated with differential neuronal activation in the paraventricular nucleus of the hypothalamus, as measured by FOS immunohistochemistry. Using triple-label immunofluorescence histochemistry, we found that a larger proportion of CRH, but not arginine vasopressin, cells are activated in the arginine vasopressin in response to both acute and chronic stress in prepubertal animals compared with adults. These data indicate that experience-dependent plasticity of the hypothalamic-pituitary-adrenal neuroendocrine axis is significantly influenced by pubertal maturation.
287 citations
TL;DR: The results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.
276 citations
TL;DR: The results suggest that a blunted HPA response to stress may play a causal role in this model of PTSD and that this susceptibility may be prevented by administration of cortisol before stress exposure.
272 citations
TL;DR: The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy, and show normal corticosterone levels at circadian trough and peak.
Abstract: Corticosteroid action in the brain is mediated by the mineralocorticoid (MR) and the glucocorticoid (GR) receptor. Disturbances in MR- and GR-mediated effects are thought to impair cognition, behavior, and endocrine control. To assess the function of the limbic MR in these processes, we inactivated the MR gene in the forebrain of the mouse using the Cre/loxP-recombination system. We screened the mice with a limbic MR deficiency in various learning and exploration tests. The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy. They exhibit a hyperreactivity toward a novel object but normal anxiety-like behavior. The behavioral changes are associated with abnormalities of the mossy fiber projection and an up-regulation of GR expression in the hippocampus. Adult mutant mice show normal corticosterone levels at circadian trough and peak. This genetic model provides important information about the consequences of a permanently altered balance between limbic MR and GR, with implications for stress-related neuroendocrine and neuropsychiatric diseases.
249 citations
TL;DR: In this paper, the authors showed that during acute stress, stress hormones may help enhance immune function by informing the immune system about impending challenges (e.g., wounding or infection) that may be imposed by a stressor.
Abstract: Delayed-type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses that, depending on the antigen, mediate beneficial (resistance to viruses, bacteria, fungi) or harmful (allergic dermatitis, autoimmunity) aspects of immunity. Contrary to the widely held notion that stress is immunosuppressive, we have shown that under certain conditions, stress can enhance immune function. DTH reactions can be studied in rats or mice by challenging the pinnae of previously sensitized animals with antigen. Studies have shown that acute stress administered immediately before antigen exposure significantly enhances skin DTH. In contrast, chronic stress significantly suppresses skin DTH. Stress-induced changes in leukocyte distribution may contribute to these bidirectional effects of stress, since acute stress induces a significant mobilization of leukocytes from the blood to the skin, whereas chronic stress suppresses leukocyte mobilization. In order to identify the hormonal mediators of the observed effects of stress, we first showed that adrenalectomy (ADX) eliminates the stress-induced enhancement of DTH. Acute administration (to ADX animals) of low doses of corticosterone and/or epinephrine significantly enhances skin DTH. In contrast, acute administration of high doses of corticosterone, low doses of dexamethasone, or chronic administration of moderate doses of corticosterone, suppress skin DTH. Thus, the timing and duration of stress may significantly affect the nature (enhancing versus suppressive) of the effects of stress on skin immune function. These results suggest that during acute stress, stress hormones may help enhance immune function by informing the immune system about impending challenges (e.g., wounding or infection) that may be imposed by a stressor (e.g., an aggressor). Thus, during acute stress, the brain may send a warning signal to the immune system, just as it does to other fight/flight systems in the body.
TL;DR: It is demonstrated that social defeat induces prolonged activation of the HPA axis and alterations in 5‐HT neurotransmission that could be of relevance to some of the pathological abnormalities observed in clinical depression.
Abstract: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) stress axis and disturbances in serotonin (5-HT) neurotransmission have been implicated in the pathogenesis of depressive disorder. Repeated social defeat of male NMRI mice has been shown to induce increases in core body temperature and corticosterone, indicative of a state of chronic stress in subordinate animals. The present study further characterised the HPA axis response to social defeat stress, and also examined hippocampal extracellular 5-HT release during the stress. Exposure to an acute social defeat elicits increases in plasma adrenocorticotrophic hormone and corticosterone levels, peaking at 15 and 30 min, respectively, and enhances corticotrophin-releasing factor (CRF) mRNA, but not arginine vasopressin (AVP) mRNA within the medial parvocellular division of the hypothalamic paraventricular nucleus. A concomitant increase in hippocampal corticosterone and 5-HT levels is observed. By contrast, although chronic social defeat is associated with greatly elevated corticosterone levels, the predominant drive appears to be via parvocellular AVP rather than CRF. Furthermore, subordinate animals allowed to recover for 9 days after chronic social defeat display an increase in immobility in the forced swimming model of depression, indicating that animals previously exposed to the homotypic defeat stress are sensitised to the behavioural effects of a novel stressor. These results demonstrate that social defeat induces prolonged activation of the HPA axis and alterations in 5-HT neurotransmission that could be of relevance to some of the pathological abnormalities observed in clinical depression.
TL;DR: This study identifies Crh as a target of MeCP2 and implicates Crh overexpression in the development of specific features of the Mecp2308/Y mouse, thereby providing opportunities for clinical investigation and therapeutic intervention in RTT.
Abstract: Rett syndrome (RTT), a postnatal neurodevelopmental disorder, is caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Children with RTT display cognitive and motor abnormalities as well as autistic features. We studied mice bearing a truncated Mecp2 allele (Mecp2308/Y mice) and found evidence of increased anxiety-like behavior and an abnormal stress response as evidenced by elevated serum corticosterone levels. We found increased corticotropin-releasing hormone (Crh) gene expression in the paraventricular nucleus of the hypothalamus, the central amygdala, and the bed nucleus of the stria terminalis. Finally, we discovered that MeCP2 binds the Crh promoter, which is enriched for methylated CpG dinucleotides. In contrast, the MeCP2308 protein was not detected at the Crh promoter. This study identifies Crh as a target of MeCP2 and implicates Crh overexpression in the development of specific features of the Mecp2308/Y mouse, thereby providing opportunities for clinical investigation and therapeutic intervention in RTT.
TL;DR: It is indicated that the inhibitory effects of DHT on HPA axis activity may be in part mediated via its conversion to 3β-diol and subsequent binding to ERβ.
Abstract: Estrogen receptor β (ERβ) and androgen receptor (AR) are found in high levels within populations of neurons in the hypothalamus. To determine whether AR or ERβ plays a role in regulating hypothalamo–pituitary–adrenal (HPA) axis function by direct action on these neurons, we examined the effects of central implants of 17β-estradiol (E2), 5α-dihydrotestosterone (DHT), the DHT metabolite 5α-androstan-3β, 17β-diol (3β-diol), and several ER subtype-selective agonists on the corticosterone and adrenocorticotropin (ACTH) response to immobilization stress. In addition, activation of neurons in the paraventricular nucleus (PVN) was monitored by examining c-fos mRNA expression. Pellets containing these compounds were stereotaxically implanted near the PVN of gonadectomized male rats. Seven days later, animals were killed directly from their home cage (nonstressed) or were restrained for 30 min (stressed) before they were killed. Compared with controls, E2 and the ERα-selective agonists moxestrol and propyl-pyrazole-triol significantly increased the stress induced release of corticosterone and ACTH. In contrast, central administration of DHT, 3β-diol, and the ERβ-selective compound diarylpropionitrile significantly decreased the corticosterone and ACTH response to immobilization. Cotreatment with the ER antagonist tamoxifen completely blocked the effects of 3β-diol and partially blocked the effect of DHT, whereas the AR antagonist flutamide had no effect. Moreover, DHT, 3β-diol, and diarylpropionitrile treatment significantly decreased restraint-induced c-fos mRNA expression in the PVN. Together, these studies indicate that the inhibitory effects of DHT on HPA axis activity may be in part mediated via its conversion to 3β-diol and subsequent binding to ERβ.
TL;DR: The studies define the critical requirement of hexose-6-phosphate dehydrogenase for 11β-HSD1 oxoreductase activity and add a new dimension to the investigation of 11 β- HSD1 as a therapeutic target in patients with the metabolic syndrome.
TL;DR: There is evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.
Abstract: The hypothalamic-pituitary-adrenal (HPA) axis is an extremely sensitive physiological system whose activation, with the consequent release of ACTH and glucocorticoids, is triggered by a wide range of psychological experiences and physiological perturbations (stressors). The HPA axis is also activated by a high number of pharmacological agents that markedly differ in structure and function, although the precise mechanisms remain in most cases unknown. Activation of the HPA axis is the consequence of the convergence of stimulatory inputs from different brain regions into the paraventricular nucleus of the hypothalamus (PVN), where the most important ACTH secretagogues (corticotrophin releasing factor, CRF, and arginin-vasopressin, AVP) are formed. Plasma levels of ACTH and corticosterone (the latter under more restricted conditions), are considered as good markers of stress for three main reasons: (a) their plasma levels are proportional to the intensity of emotional and systemic stressors, (b) daily repeated exposure to a stressor usually resulted in reduced ACTH response to the same stressor, that is termed adaptation or habituation; and (c) chronic exposure to stressful situations results in tonic changes in the HPA axis that can be used as indices of the accumulative impact of these situations. These changes can be evaluated under resting conditions (i.e. adrenal weight, CRF and AVP gene expression in the PVN) or after some challenges (administration of CRF, ACTH or dexamethasone) that are classical endocrinological tests. There is also evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.
TL;DR: Results suggest corticosterone is important in sensitive-period termination and developmental emergence of olfactory fear conditioning, acting via the amygdala as a switch between fear and attraction.
Abstract: Rat pups must learn maternal odor to support attachment behaviors, including nursing and orientation toward the mother. Neonates have a sensitive period for rapid, robust odor learning characterized by increased ability to learn odor preferences and decreased ability to learn odor aversions. Specifically, odor-0.5 mA shock association paradoxically causes an odor preference and coincident failure of amygdala activation in pups until postnatal day 10 (P10). Because sensitive-period termination coincides with a declining "stress hyporesponsive period" when corticosterone release is attenuated, we explored the role of corticosterone in sensitive-period termination. Odor was paired with 0.5 mA shock in either sensitive-period (P8) or postsensitive-period (P12) pups while manipulating corticosterone. We then assessed preference/aversion learning and the olfactory neural circuitry underlying its acquisition. Although sensitive-period control paired odor-shock pups learned an odor preference without amygdala participation, systemic (3 mg/kg, i.p.; 24 h and 30 min before training) or intra-amygdala corticosterone (50 or 100 ng; during training) permitted precocious odor-aversion learning and evoked amygdala neural activity similar to that expressed by older pups. In postsensitive-period (P12) pups, control paired odor-shock pups showed an odor aversion and amygdala activation, whereas corticosterone-depleted (adrenalectomized) paired odor-shock pups showed odor-preference learning and activation of an odor learning circuit characteristic of the sensitive period. Intra-amygdala corticosterone receptor antagonist (0.3 ng; during training) infused into postsensitive-period (P12) paired odor-shock pups also showed odor-preference learning. These results suggest corticosterone is important in sensitive-period termination and developmental emergence of olfactory fear conditioning, acting via the amygdala as a switch between fear and attraction. Because maternal stimulation of pups modulates the pups' endogenous corticosterone, this suggests maternal care quality may alter sensitive-period duration.
TL;DR: Results show that high levels of corticosterone either before or after progenitor labeling discouraged the acquisition of neuronal fate, and the total number of neurons formed resulting from different corticoid treatments was estimated.
TL;DR: Evidence is provided that, as found with other emotionally arousing tasks, the enhancing effects of corticosterone on memory consolidation of auditory-cue fear conditioning require posttraining noradrenergic activity within the BLA.
TL;DR: It is demonstrated that, although acute social defeat has similar effects on temperature and HPA activity, repeated exposure to social stress has divergent effects on H PA activity compared to body temperature and that dampened weight gain produced by repeated social stress cannot be fully explained by changes in food intake.
Abstract: These present studies aimed to compare changes in hypothalamic-pituitary-adrenal (HPA) activity and body temperature in response to acute social defeat, to repeated social stress and to novel restraint after repeated stress, as well as to assess effects on metabolic parameters by measuring body weight gain and food and water intake We found that social defeat produced a marked increase in both adrenocorticotrophic hormone and corticosterone compared to placement in a novel cage Similarly, body temperature was also increased during social defeat and during 30 min of recovery from defeat We then examined the effects of 6 days of repeated social stress and observed minimal HPA responses to repeated social stress compared to control rats These neuroendocrine responses were contrasted by robust increases in body temperature during stress and during recovery from stress during 6 days of repeated stress However, in response to novel restraint, repeatedly stressed rats displayed facilitated body temperature responses compared to controls, similar to our previous findings with HPA activity Food intake was increased during the light period during which defeat took place, but later intake during the dark period was not affected Repeated stress decreased body weight gain in the dark period but food intake was increased overall during the 6 days of repeated stress in the light period As a result, repeated stress increased cumulative food intake during the light period in the stressed rats but these relatively small increases in food intake were unable to prevent the diminished total weight gain in repeatedly stressed rats Overall, the results demonstrate that, although acute social defeat has similar effects on temperature and HPA activity, repeated exposure to social stress has divergent effects on HPA activity compared to body temperature and that dampened weight gain produced by repeated social stress cannot be fully explained by changes in food intake
TL;DR: Although cortic testosterone and antidepressants both modulate brain-derived neurotrophic factor expression, and antidepressants reverse the corticosterone-induced brain- derived neurotrophicFactor decrease, antidepressants and cortic hormone differ in how they regulate the expression of brain- derive neurotrophicfactor exon(s).
TL;DR: Both the anxiogenic behaviour of PS males and females and the learning deficit in males were completely abolished by adrenalectomy, showing that excess stress-induced COR can alter the programming of the foetal brain and predispose it to alterations in behaviour that are gender specific.
TL;DR: The effects of prenatal stress on fetal growth, stress-induced corticosterone secretion, brain cell proliferation, caspase-3-like activity and brain-derived neurotrophic factor protein content in newborn Fischer 344 rats are studied.
TL;DR: The consistent gender differences confirm and expand existing results showing altered anxiety and stress reactivity in male and female rats.
TL;DR: Data demonstrate a novel role for NPS in the stimulation of the HPA axis and the effect of intracerebroventricular administration of NPS on behavior, regulation of theHPA axis, and food intake.
Abstract: Neuropeptide S (NPS) is a recently discovered peptide shown to be involved in the modulation of arousal and fear responses. It has also been shown that lateral ventricle administration of NPS causes a significant decrease in food intake. Neuropeptides involved in the modulation of arousal have been shown to be involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis and food intake. In this study, we have examined the effect of intracerebroventricular (ICV) administration of NPS on behavior, regulation of the HPA axis, and food intake. ICV NPS significantly increased plasma ACTH and corticosterone 10 and 40 min after injection, respectively. A single ICV injection of NPS caused a significant increase in rearing activity as well as ambulatory movement for up to 45 min after injection. We then studied the effect of paraventricular nucleus (PVN) administration of NPS on the regulation of the HPA axis, behavior, and food intake. There was a significant increase in plasma ACTH and corticosterone after a single NPS PVN injection. Incubation of hypothalamic explants with increasing concentrations of NPS caused a significant increase in CRH and arginine vasopressin release. In addition, PVN administration of NPS dose-dependently inhibited food intake in the first hour after injection, although no effect on food intake was seen after this time. PVN administration of NPS caused a significant increase in rearing activity. These data demonstrate a novel role for NPS in the stimulation of the HPA axis.
TL;DR: In this article, the glucocorticoid receptor antagonist mifepristone has been shown to rapidly and effectively ameliorate symptoms of psychotic major depression in rats.
Abstract: The glucocorticoid receptor antagonist mifepristone has been shown to rapidly and effectively ameliorate symptoms of psychotic major depression. To better understand its mechanism, we investigated mifepristone's cellular effects, and found that it rapidly reversed a chronic corticosterone-induced reduction of adult neurogenesis in rats. Unlike other antidepressants, mifepristone is particularly potent in a high corticosterone environment. These data indicate that similarly to its clinical efficacy, mifepristone's effects on adult neurogenesis are rapid and positive, and may therefore be important for its mechanism of action.
TL;DR: The mechanisms by which adrenal cortical hormones produce their important effects on their specific target cells, lymphocytes are focused on.
Abstract: This presentation is designed primarily to review the interrelationship between the influence of certain corticosteroids on lymphatic tissue and, in turn, lymphatic tissue influences on the biotransformation of adrenal cortical hormones. New data has not been introduced here; rather, emphasis has been placed on presenting a brief account of the work performed in our laboratory. The details of the investigations presented here are given in several reviews\" as well as in more detailed reports of certain phases of this work which are referenced in the reviews. The phenomenon of adrenal-mediated stressful involution of lymphatic organs is well documented and has been described many times. Emphasis here, then, is to be placed on the mechanisms by which adrenal cortical hormones produce their important effects on their specific target cells, lymphocytes.
TL;DR: In this paper, the influence of noise stress on working and reference memory error in rats was evaluated by radial eight-arm maze experiment and it was shown that after noise-stress exposure, 100 dBA/4h per day for 30 days, working and relation memory error increased significantly (P < 0.05).
TL;DR: The data suggest that chronic stress selectively targets brain circuits responsible for integration of psychogenic stimuli, resulting in decreased HPA axis responsiveness, possibly mediated in part by transitory alterations in PVN CRH expression.
Abstract: Chronic stress induces both functional and structural adaptations within the hypothalamo-pituitary-adrenocortical (HPA) axis, suggestive of long-term alterations in neuroendocrine reactivity to subsequent stressors. We hypothesized that prior chronic stress would produce persistent enhancement of HPA axis reactivity to novel stressors. Adult male rats were exposed to chronic variable stress (CVS) for 1 wk and allowed to recover. Plasma ACTH and corticosterone levels were measured in control or CVS rats exposed to novel psychogenic (novel environment or restraint) or systemic (hypoxia) stressors at 16 h, 4 d, 7 d, or 30 d after CVS cessation. Plasma ACTH and corticosterone responses to psychogenic stressors were attenuated at 4 d (novel environment and restraint) and 7 d (novel environment only) recovery from CVS, whereas hormonal responses to the systemic stressor were largely unaffected by CVS. CRH mRNA expression was up-regulated in the paraventricular nucleus of the hypothalamus (PVN) at 16 h after cessation of CVS, but no other alterations in PVN CRH or arginine vasopressin mRNA expression were observed. Thus, in contrast to our hypothesis, reductions of HPA axis sensitivity to psychogenic stressors manifested at delayed recovery time points after CVS. The capacity of the HPA axis to respond to a systemic stressor appeared largely intact during recovery from CVS. These data suggest that chronic stress selectively targets brain circuits responsible for integration of psychogenic stimuli, resulting in decreased HPA axis responsiveness, possibly mediated in part by transitory alterations in PVN CRH expression.
TL;DR: The results suggest that concurrent manipulation of the HPA axis might improve sensitivity to selective serotonin reuptake inhibitors in some treatment-resistant patients and altered neurogenesis in the dentate gyrus in the male rat.