Reduced Corticosterone Levels Research Articles

Hypothalamic regulation of energy balance: a key role for DICER miRNA processing in arcuate POMC neurons

Hypothalamic regulation of energy balance: a key role for DICER miRNA processing in arcuate POMC neurons

Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats

Ethnopharmacological relevanceWithania somnifera (WS) root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer and anti-stress agent. Aim of the studyTo evaluate the neuroprotective and prophylactic potential of WS root extract in ameliorating hypobaric hypoxia (HH) induced memory impairment and to explore the underlying molecular mechanism. Materials and methodsWS root extract was administered to male Sprague Dawley rats during a period of 21 days pre-exposure and 07 days exposure to a simulated altitude of 25,000ft. Spatial memory was assessed by Morris Water Maze. Neurodegeneration, corticosterone, acetylcholine (Ach) levels, acetylcholine esterase (AchE) activity, oxidative stress markers and nitric oxide (NO) concentration were assessed in the hippocampus. Synaptic and apoptotic markers were also investigated by immunoblotting. To study the role of NO in regulating corticosterone mediated signaling, the neuronal nitric oxide synthase (n-NOS) inhibitor, l-Nitro-arginine methyl ester (l-Name) and NO agonist sodium nitroprusside (SNP) were administered from 3rd to 7th day of hypoxic exposure. ResultsAdministration of WS root extract prevented HH induced memory impairment and neurodegeneration along with decreased NO, corticosterone, oxidative stress and AchE activity in hippocampal region. Inhibition of NO synthesis by administration of l-Name reduced corticosterone levels in hippocampus during hypoxic exposure while co-administration of corticosterone increased neurodegeneration. Administration of sodium nitroprusside (SNP) along with WS root extract supplementation during hypoxic exposure increased corticosterone levels and increased the number of pyknotic cells. ConclusionWS root extract ameliorated HH induced memory impairment and neurodegeneration in hippocampus through NO mediated modulation of corticosterone levels.

123. Corticosteroids, but not catecholamines, mediate stress- and surgery-induced suppression of plasma IL-12 levels in rats: A second-phase response of stress-induced immune perturbations

We recently reported that various stress paradigms suppress plasma IL-12 levels. The aim of this study was to elucidate potential neuroendocrine mediating mechanisms. Administration of prostaglandin-E2, epinephrine, and corticosterone, significantly reduced plasma IL-12 levels. However, when subjecting animals to stress or surgery, only the glucocorticoid-receptor blocker, mifepristone, and the COX-2 inhibitor, etodolac, but not α- or β-adrenergic blockers, attenuated the reduction of plasma IL-12 levels. As epinephrine administration did reduce IL-12 levels, we subjected adrenalectomized and sham-operated rats to epinephrine and/or corticosterone administration. While corticosterone reduced IL-12 levels in both conditions, epinephrine did so only in sham operated animals, indicating that its effects are mediated through elevated endogenous corticosterone levels, which we confirmed. In addition, blockade of prostaglandin production during surgery also reduced corticosterone levels, suggesting that at least some of the effects of prostaglandin are corticosterone-mediated. In accordance, but contrary to some reports, our in vitro studies indicated that corticosterone, but not prostaglandin-E2 or epinephrine, reduced spontaneous and induced IL-12 production levels. We thus hypothesize that stress-induced immune perturbations rely on two mechanisms: One mediated through activation of short-lasting processes by catecholamines and/or prostaglandins, and a second leading to long-lasting perturbations through glucocorticoids. IL-12 has a long half-life time and is prominent in inducing Th1 differentiation – a long lasting process that, as observed herein, is indeed suppressed through elevated corticosteroids, but not catecholamines.

Decreased Fecal Corticosterone Levels Due to Domestication: A Comparison Between the White‐Backed Munia (Lonchura striata) and Its Domesticated Strain, the Bengalese Finch (Lonchura striata var. domestica) With a Suggestion for Complex Song Evolution

The Bengalese finch (BF; Lonchura striata var. domestica) is a domesticated strain of the white-backed munia (WBM; Lonchura striata). Environmental stresses activate the hypothalamic-pituitary-adrenal (HPA) axis and release corticosterone (CORT). We hypothesized that domesticated songbirds have reduced CORT levels because of reduced levels of environmental stresses (compared to wild conditions) and reductions in the role of CORT, which is necessary for survival in the wild. However, no study has examined the effects of domestication on songbird CORT levels. To explore the domestication effects, we compared CORT levels between domesticated BFs and their wild ancestors WBMs. We also compared CORT levels between bought and aviary-raised BFs, and between wild-caught and captive-raised WBMs to examine the influence of being raised. However, blood collection causes stress, which affects endocrine dynamics and makes continuous sampling difficult in small birds. Therefore, we used a non-invasive method to measure fecal CORT. Parallelism between diluted fecal extracts and a CORT standard, extraction efficiency, and ACTH challenge demonstrated the effectiveness of this method. This study demonstrates that BFs have lower fecal CORT than do WBMs, regardless of whether the WBMs were wild-caught or captive-raised. In addition, BFs sing more complex songs than WBMs. Considerable evidence suggests that song complexity is related to CORT levels. Previously, we found that the corticosteroid receptors were expressed in song-control areas of the BF brain. Based on these results, we hypothesize that reduced CORT levels through domestication might be one factor allowing for the development of more complex songs in BFs.

A New Anti-Depressive Strategy for the Elderly: Ablation of FKBP5/FKBP51

The gene FKBP5 codes for FKBP51, a co-chaperone protein of the Hsp90 complex that increases with age. Through its association with Hsp90, FKBP51 regulates the glucocorticoid receptor (GR). Single nucleotide polymorphisms (SNPs) in the FKBP5 gene associate with increased recurrence of depressive episodes, increased susceptibility to post-traumatic stress disorder, bipolar disorder, attempt of suicide, and major depressive disorder in HIV patients. Variation in one of these SNPs correlates with increased levels of FKBP51. FKBP51 is also increased in HIV patients. Moreover, increases in FKBP51 in the amygdala produce an anxiety phenotype in mice. Therefore, we tested the behavioral consequences of FKBP5 deletion in aged mice. Similar to that of naïve animals treated with classical antidepressants FKBP5−/− mice showed antidepressant behavior without affecting cognition and other basic motor functions. Reduced corticosterone levels following stress accompanied these observed effects on depression. Age-dependent anxiety was also modulated by FKBP5 deletion. Therefore, drug discovery efforts focused on depleting FKBP51 levels may yield novel antidepressant therapies.

Experimentally reduced corticosterone release promotes early breeding in black-legged kittiwakes

Breeding at the right time is important for successful reproduction. In birds, stressful environmental conditions are known to delay the timing of breeding but the underlying mechanisms are poorly understood. The stress hormone corticosterone appears to be a good candidate for mediating egg-laying date according to early environmental conditions and physiological state. By experimentally reducing the release of corticosterone in black-legged kittiwakes during the pre-laying period, we tested whether egg-laying date was mechanistically linked to corticosterone levels. Male and female kittiwakes were implanted with a low dose of exogenous corticosterone to inhibit endogenous corticosterone production. According to our predictions, the experimental reduction of corticosterone release was paralleled by a significant advancement of egg laying in females (around 4 days earlier). In addition, females with experimentally reduced corticosterone release gained mass during the pre-laying period compared with controls. Ultimately, the advancement of egg laying in females with experimentally reduced corticosterone levels was associated with an enhanced breeding success. This effect was strongly sex specific. In corticosterone-treated male kittiwakes, egg-laying date and reproductive success were not affected, but breeding probability was lower than in controls. This corticosterone treatment did not influence immediate clutch size, or return rate and breeding decision the following year. Our results support the hypothesis that corticosterone secretion during the pre-laying period mediates the timing of breeding in this long-lived seabird, possibly through the dynamics of energy reserves.

State dependent effects of elevated hormone: Nest site quality, corticosterone levels and reproductive performance in the common eider

Nest shelter in incubating birds is of major importance in providing protection against unfavourable conditions such as harshness of the environment and exposure to predators. We examined the link between nest shelter, baseline corticosterone (CORT) levels and hatching success in common eiders ( Somateria mollissima) incubating at nest sites with different levels of shelter. Since more sheltered nest sites could be occupied by better-quality females, we also used an experimental manipulation of nest shelter to separate the effects of the physical attributes of the nest site from those of individual quality. We compared birds with naturally sheltered nests, exposed nests and exposed nests provided with artificial nest shelters and measured clutch size, body condition, CORT levels at the end of incubation and hatching success. If nest shelter reduces CORT levels, we predicted that CORT levels would be highest at the least sheltered sites, and that the provision of artificial shelter would reduce CORT levels. We found that nest shelter was not related to CORT levels in incubating eiders. Nest shelter, however, affected body condition, with females at exposed sites losing more body mass during incubation than females at naturally and artificially sheltered nests. Interestingly however, in those birds nesting at the exposed sites, with and without artificial shelter, those with the highest CORT levels had the lowest hatching success. This relationship was not evident in females nesting at naturally sheltered sites. These results suggest that the level of nest shelter does not directly affect CORT levels in females. Instead, we suggest that the relationship between CORT levels and hatching success is state-dependent. Exposed sites are occupied by individuals that laid smaller clutches, and hence are likely to be of lower quality, and the negative effects of elevated CORT on hatching success are more pronounced in these females.

The effects of antalarmin on behavioural and biochemical aspects of chronic nicotine administration and acute nicotine withdrawal in rats

Event Abstract Back to Event The effects of antalarmin on behavioural and biochemical aspects of chronic nicotine administration and acute nicotine withdrawal in rats M. Palotai1, Z. Bagosi1*, K. Csabafi1 and G. Szabó1 1 University of Szeged, Department of Pathophysiology, Hungary Introduction: In the present experiments we studied the actions of selective CRF1 receptor antagonist antalarmin on the hyperactivity elicited by chronic nicotine treatment and the hypoactivity induced by consecutive nicotine withdrawal in rats. Methods: 2 mg/kg nicotine was injected intraperitoneally for 7 days, 4 times/day and 0,1 mg/2 ml antalarmin was administered intracerebroventricularly on the 8th and the 9th day’s morning. An in vivo conducta system based upon open field test was used to study horizontal activity, vertical activity and total drive of the animals. An in vitro superfusion system was used to determine striatal dopamine and amygdalar GABA release from brain slices; meanwhile plasma corticosterone was extracted and detected by a chemofluorescent assay from trunk blood. Results: Antalarmin inhibited considerably the anxiogenic behaviour and the elevated plasma corticosterone level, striatal dopamine and amygdalar GABA releases observed at 12 hours after the last nicotine administration. It also antagonized remarkably the anxiolytic behaviour and the reduced corticosterone level observed at 24 hours after the last nicotine administration. However the changes of dopamine release from the striatum and the GABA release from the amygdala were insignificant at this time. Conclusion: Antalarmin ameliorates most of the behavioural and biochemical consequences of chronic nicotine administration and consecutive nicotine withdrawal. Acknowledgements This work was supported by the following grants: ETT 355-08/2009 and TÁMOP 4.2.1B. Keywords: Behaviour and cognition, Neuroscience Conference: 13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011. Presentation Type: Abstract Topic: Behaviour and cognition Citation: Palotai M, Bagosi Z, Csabafi K and Szabó G (2011). The effects of antalarmin on behavioural and biochemical aspects of chronic nicotine administration and acute nicotine withdrawal in rats. Front. Neurosci. Conference Abstract: 13th Conference of the Hungarian Neuroscience Society (MITT). doi: 10.3389/conf.fnins.2011.84.00014 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Mar 2011; Published Online: 23 Mar 2011. * Correspondence: Dr. Z. Bagosi, University of Szeged, Department of Pathophysiology, Szeged, Hungary, bagosi@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers M. Palotai Z. Bagosi K. Csabafi G. Szabó Google M. Palotai Z. Bagosi K. Csabafi G. Szabó Google Scholar M. Palotai Z. Bagosi K. Csabafi G. Szabó PubMed M. Palotai Z. Bagosi K. Csabafi G. Szabó Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effects of Melissa officinalis L. (Lemon Balm) Extract on Neurogenesis Associated with Serum Corticosterone and GABA in the Mouse Dentate Gyrus

Lemon balm, leaves of Melissa officinalis L., has been used for anti-anxiety and spasmolytics. We observed the extract of Melissa officinalis L. (MOE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of middle-aged mice (12 months of age) using Ki67 and doublecortin (DCX), respectively. We also observed changes in corticosterone, GAD67 and GABA-transaminase (GABA-T) to check their possible mechanisms related to neurogenesis. We administered 50 or 200 mg/kg MOE to the animals once a day for 3 weeks. For labeling of newly generated cells, we also administered 5-bromodeoxyuridine (BrdU) twice a day for 3 days from the day of the first MOE treatment. Administration of 50 or 200 mg/kg MOE dose-dependently increased Ki67 positive nuclei to 244.1 and 763.9% of the vehicle-treated group, respectively. In addition, 50 or 200 mg/kg MOE significantly increased DCX positive neuroblasts with well-developed (tertiary) dendrites. Furthermore, MOE administration significantly increased BrdU/calbindin D-28 k double labeled cells (integrated neurons into granule cells in the DG) to 245.2% of the vehicle-treated group. On the other hand, administration of MOE reduced corticosterone levels in serum and decreased GABA-T levels in the DG homogenates. These results suggest that MOE increases cell proliferation, neuroblast differentiation and integration into granule cells by decreasing serum corticosterone levels as well as by increasing GABA levels in the mouse DG.

Corticosterone evaluation in Wistar rats infected with the Y strain of Trypanosoma cruzi during the chronic phase

Understanding the mechanisms responsible for mediating the effects of stress on Trypanosoma cruzi infection is crucial for determining the full impact of stress on Chagas’ disease and for devising effective interventions. Dehydroepiandrosterone (DHEA), a steroid hormone synthesized from pregnenolone, is secreted by the adrenal cortex in response to stress. Although its physiologic role has not been fully defined, DHEA has been shown to modulate immune function. In the present study, we evaluated the levels of corticosterone and the ability of T. cruzi infection to modulate the expression of Th2 cytokines in Wistar rats with chronic Chagas’ disease submitted to repetitive stress. The animals submitted to stress displayed enhanced levels of corticosterone as compared to control counterparts. Stress and infection triggered the most elevated concentrations of corticosterone. DHEA significantly reduced corticosterone levels for infected and stressed animals with DHEA. The infected animals displayed enhanced levels of IL-10 and IL-4 as compared to control ones. Stress combined with infection triggered the higher levels of IL-10 and IL-4. DHEA alone and combined with infection and stress significantly increased IL-10 and IL-4 levels. Then, this study might provide additional clues about factors that regulate some of the immunoregulatory aspects of T. cruzi infection and might offer new opportunities for therapeutic interventions.

Application of a naturalistic psychogenic stressor in periadolescent mice: effect on serum corticosterone levels differs by strain but not sex

BackgroundAs a first step in determining whether psychogenic stressors might be incorporated into periadolescent mouse models of stress, we evaluated whether a commonly used psychogenic stressor, exposure to red fox urine, alters serum corticosterone levels in periadolescent C57BL/6J and DBA/2J mice.FindingsIn a 1-day experiment, forty-eight 38-day-old C57BL/6J (N = 12 males; N = 12 females) and DBA/2J (N = 12 males; N = 12 females) mice were exposed to 10-min of red fox urine via cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice) or to a non-saturated cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice). All mice were sacrificed 15-min after cotton ball exposure and serum was collected for corticosterone assessment. Overall, there was a main effect for strain such that C57BL/6J male and female mice displayed higher corticosterone levels than did male and female DBA/2J mice. There were no main effects for sex or odor exposure. However, there was a significant strain by odor exposure interaction, whereby, within odor-exposed mice, DBA/2J mice displayed lower corticosterone levels (ng/mL) compared to C57BL/6J mice, regardless of sex. Further, among DBA/2J mice, predator odor exposure reduced corticosterone levels compared to no odor exposure.ConclusionsFindings indicate that mouse strain, but not sex, may play an important role in the efficacy of a predator odor among periadolescent mice.

Interspecific variation in fear responses predicts urbanization in birds

Urbanization and domestication share features in terms of characters that are favored by selection. These include loss of fear of humans, reduced corticosterone levels, prolonged breeding seasons, and several others. Here, I test the hypothesis that urbanization results from differential colonization of urban areas by species with heterogeneous levels of fear in the ancestral rural populations, followed by a reduction in variance in fear responses with a subsequent increase in diversity of fear responses as urban populations become adapted to the urban environment. Using information on variance in flight initiation distances (FIDs) when approached by a human, I show that rural populations of birds characterized by short mean flight distances and large variances in flight distances differentially colonized urban areas. As a consequence of this urban invasion, urban populations lost variation in FID. The variance in FID was initially larger in rural than in urban populations but eventually became larger in urban populations with time since urbanization. This secondary increase in variance in FID of urban populations was associated with an increase in population density of urban populations, suggesting that as birds became adapted to urban areas, they secondarily gained variance in behavioral flexibility.

The role of pituitary glucocorticoid receptors in hypothalamic-pituitary-adrenal axis regulation following chronic social stress

One of the main physiological systems mediating adaptation to stressful stimuli is the hypothalamic-pituitary-adrenal (HPA) axis. Negative feedback control through glucocorticoids (GCs) is an important mechanism to restore homeostasis after HPA axis activation. GCs act via two receptor types, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). While MRs have been shown to regulate basal and circadian GC levels, GRs play a modulatory role in stressful situations, both acute and chronic. However, the contribution of different physiological subregions in negative feedback control is largely unknown. In this study we investigate the role of negative feedback via GCs on the level of the pituitary by utilizing pituitary-specific conditional GR knockout mice. Following 3 weeks of chronic social defeat, we observed an increase in anxiety-related behavior as well as elevated basal corticosterone levels in control mice. Mice with a GR deficiency in the pituitary show a diminished reaction to chronic stress as indicated by reduced corticosterone levels both basal and after acute stress. These findings are supported by behavioral data that showed decreased anxiety-like behaviour in knockouts compared to controls. In conclusion, we suggest that a lack of pituitary GRs results in a protective effect towards neuroendocrine and behavioral consequences of chronic stress. We hypothesize that this might be due to alterations in postnatal development of GR knockout mice.

Effects of antalarmin and nadolol on the relationship between social stress and pulmonary metastasis development in male OF1 mice

It has been found that acute social stress in male OF1 mice produced a general immunosuppression and increased B16F10 tumor development. This study examined the effects of blocking either the hypothalamic–pituitary–adrenocortical (HPA) axis or the sympathetic adrenomedullary (SAM) system on the impact of such stress on tumor development. Naive male OF1 mice were individually housed for 12 days before being inoculated with tumor cells or vehicle. Six days later, tumor-bearing mice were inoculated with antalarmin (a corticotropin-releasing factor receptor antagonist), nadolol (a beta-adrenergic antagonist) or vehicle. All these mice were subjected to social stress by pairing them for 24 h with counterparts selected for their high and homogeneous levels of aggressiveness. The pairs were only in physical contact for three 5-min periods, being in sensory contact for the rest of this period. One hour after social stress, serum corticosterone and IFN- gamma levels were analyzed in each experimental group. Fifteen days later, lungs were removed to determine the number of metastatic foci with their areas, and blood samples were taken to assess serum titers of corticosterone and IFN- gamma. Both antalarmin and nadolol-treated mice developed significantly fewer metastatic foci with smaller areas than vehicle-treated subjects although only the group treated with antalarmin had reduced corticosterone levels. This study confirms that social stress has complex effects on immune system and tumor development that are not simply linked to corticosterone titers.

Reduced Behavioral Response to Gonadal Hormones in Mice Shipped during the Peripubertal/Adolescent Period

Animals shipped from commercial suppliers to laboratories are exposed to a wide variety of stressors. Female C57Bl6/J mice shipped during the peripubertal/adolescent period (6 wk old) display lower levels of female sexual behavior in response to estradiol and progesterone injections after ovariectomy when tested in adulthood than female mice shipped in adulthood (12 wk old). These shipping-induced reductions in female sexual behavior appear to be limited to a vulnerable period around the time of puberty. Likewise, male mice shipped at 6 wk of age express lower levels of masculine sexual behavior in response to testosterone treatment as adults than do mice shipped when 12 wk old. RIA of corticosterone levels in response to behavior testing revealed that, upon first exposure to testing, mice shipped at 6 wk of age have reduced corticosterone levels. These results suggest that during the peripubertal/adolescent period, mice of both sexes are susceptible to the effects of stressors associated with shipping. Furthermore, they suggest that stress during this period has enduring, negative influences on behavioral responses to estradiol and progesterone in females and to testosterone in males, and it induces changes in response of the hypothalamic-pituitary-adrenal axis. These results suggest that age at shipping is a critical variable that may influence many endocrinological studies, and they suggest that the peripubertal/adolescent period is a period of vulnerability to some stressors.

Glucocorticoid signaling and exercise-induced downregulation of the mineralocorticoid receptor in the induction of adult mouse dentate neurogenesis by treadmill running

Physical exercise is known to promote adult neurogenesis, although the underlying mechanisms remain unclear. Glucocorticoid (corticosterone in rodents) is a factor that is known to affect neurogenesis. As physical exercise modulates corticosterone secretion, we hypothesized that corticosterone signaling is involved in exercise-induced adult neurogenesis. We chose treadmill running (TR) to accurately define the intensity and duration of exercise. Our results showed that 5 weeks of TR increased the doublecortin (DCX)-positive neuronal progenitor cells (NPCs) in adult hippocampus and transiently increased the serum corticosterone level at the end of the TR protocol. This protocol reduced the levels of hippocampal mineralocorticoid receptor (MR); however, glucocorticoid receptor levels were unaltered. We then investigated whether reducing corticosterone levels by bilateral adrenalectomy (ADX) attenuated the TR-enhanced adult neurogenesis. Our results showed that ADX not only blocked the TR-induced downregulation of MR, but also reduced the number of TR-enhanced NPCs. In order to examine the role of MR downregulation in TR-induced adult neurogenesis, animals were treated repeatedly with a selective MR antagonist, spironolactone, for 3 weeks. The results revealed that spironolactone increased the number of spontaneously occurring and TR-induced NPC in the dentate area. Further analysis revealed that spironolactone treatment did not alter precursor cell proliferation, but increased the number of DCX-positive NPCs, suggesting that blockage of MR signaling either facilitates the differentiation of progenitor cells towards neurons and/or enhances the survival of NPCs. Taken together, the data indicated that induction of NPCs in the dentate area of adult hippocampus by TR is partly due to the downregulation of glucocorticoid/MR signaling, which subsequently enhances differentiation along a neuronal lineage and/or NPC survival.

Binge-type eating attenuates corticosterone and hypophagic responses to restraint stress

Binge eating has been associated with stress responses. Data in rats suggest that activation of the hypothalamic-pituitary-adrenal (HPA) axis is suppressed by consumption of a high sucrose diet, and is increased with exposure to a high fat diet. Additionally, the choice to consume a highly palatable food following exposure to a stressor results in reduced corticosterone levels. To test the effects of intermittent access to a high sugar/high fat food on stress hormone levels, rats were given either unrestricted (UR) access to a sucrose-vegetable shortening mixture (SVS) or 2 hour SVS access 7 days (7D) or 3 days (3D) per week for 4 weeks. Rats on the UR and 3D schedules consumed significantly more calories per day than did controls with no access to SVS, and the 7D and 3D rats consumed as many SVS calories in the 2 hour access period as did the UR rats with 24 hour access to SVS. After 4 weeks of access to SVS (UR, 7D, and 3D), rats were briefly restrained. Control and UR rats had elevated corticosterone during and following restraint, whereas there were no differences in corticosterone levels of 7D and 3D rats in response to restraint, as compared to baseline. Post-restraint consumption of chow was significantly decreased in all groups, and consumption of SVS was reduced in the UR, but not the 7D and 3D rats. These data demonstrate that intermittent access to SVS dampens the corticosterone response to restraint stress and that stressful events do not induce bingeing in non-bingeing animals with access to a high sucrose/high fat food.

Neonatal handling increases cardiovascular reactivity to contextual fear conditioning in borderline hypertensive rats (BHR)

Much research has demonstrated that events occurring in early life can have a profound influence on future biobehavioral responses to stressful and emotion provoking situations. The purpose of these studies was to determine the effects of an early environmental manipulation, handling (HAN) on cardiovascular (CV) reactivity, freezing behavior and corticosterone (CORT) responses to contextual fear conditioning in the borderline hypertensive rat (BHR),which is susceptible to environmental stressors. HAN subjects were separated from the nest for 15 min/day on post-natal days 1–14, while non-handled (NON-HAN) controls remained in the home cage. Adult subjects were exposed to the contextual fear conditioning procedure and returned to the chamber 24 h later for a 10 min test period. HAN subjects displayed significantly more freezing behavior compared to NON-HAN(92% ± 2.2 vs 80.7% ± 5.7, p < .05). Although resting MAP did not differ between groups, HAN subjects had increased MAP reactivity when re-exposed to the chamber. In addition, HAN subjects had significantly lower CORT levels at the end of the 10 min test period (174.2 ± 9 ng/ml vs 237.2 ± 12.9 ng/ml, p < .05). In the second experiment, CORT responses to 60 min of restraint stress and recovery following return to the home cage were assessed in separate groups of HAN and NON-HAN subjects. HAN subjects showed reduced CORT levels in response to acute restraint stress. These results indicate that neonatal handling can modulate biobehavioral responses to contextual fear conditioning in BHR and may suggest a useful model with which to study emotionality and susceptibility to CV disease.

Brief and long maternal separations decrease corticosterone secretion in a lupus-prone strain: Dissociation from disease-related parameters

Neonatal manipulations are known to alter the activity of the immune system and the hypothalamus–pituitary–adrenal (HPA) axis. This study was performed in order to examine whether brief and long maternal separations (BMS and LMS, respectively) interfere with the onset and development of murine lupus in NZB/NZWF1 females, and to determine whether the pattern of corticosterone (CORT) secretion throughout life is associated to the expression of the disease. Maternal separation was performed daily during postnatal days 1–14, lasting 15 min in the BMS group and 3 h in the LMS group. Blood was sampled from the retro-orbital plexus on the 9th week, and every other week, from 10th to 34th weeks of life, for detection of anti-nuclear antibodies (ANA) and anti-double-strand DNA (anti-dsDNA) antibodies, and for determination of CORT serum levels. Urine samples were collected on the 21st, 27th, 33rd and 37th weeks of life. There were no group differences in regard to disease-related parameters, but LMS females presented a tendency for late onset of anti-dsDNA antibodies. BMS and LMS mice exhibited reduced CORT levels compared to non-manipulated (NM) animals. There was a strong negative correlation between total mean CORT concentration and onset of ANA, and a strong positive correlation between total mean CORT concentration and life span only in the NM group. Neonatal manipulations appeared to eliminate these correlations; hence, both BMS and LMS modified basal CORT secretion and the association between glucocorticoids and immune activity in the NZB/NZWF1 mouse strain.

CRF 1 Not Glucocorticoid Receptors Mediate Prepulse Inhibition Deficits in Mice Overexpressing CRF

Both corticotropin-releasing factor (CRF) and glucocorticoid receptors (GR) are implicated in the psychotic symptoms of psychiatric disorders. Correspondingly, it is of interest to determine their respective involvement in the sensorimotor gating deficits displayed by transgenic mice overexpressing CRF. These mice reveal lifelong elevations of CRF and corticosterone levels. Effects of the GR antagonists ORG34517 (5-45 mg/kg by mouth [PO]) and mifepristone (5-45 mg/kg PO) and the CRF(1) receptor antagonists CP154,526 (20-80 mg/kg intraperitoneally [IP]) and DMP695 (2.5-40.0 mg/kg IP) on prepulse inhibition (PPI) of the acoustic startle response were studied in mice overexpressing CRF and in their wild-type littermates. In addition, PPI was measured in both genotypes 2 weeks after adrenalectomy with or without exogenous corticosterone administration via subcutaneous pellet implant (20 mg corticosterone). ORG34517 and mifepristone did not influence perturbation of PPI in mice overexpressing CRF; reducing corticosterone levels by adrenalectomy likewise did not improve PPI. Further, elevation in corticosterone levels by pellet implantation did not disrupt PPI in wild-type mice. Conversely, both CRF(1) receptor antagonists, CP154,526 (40-80 mg/kg IP) and DMP695 (40 mg/kg IP), significantly restored PPI in CRF-overexpressing mice. Sustained overactivation of CRF(1) receptors rather than excessive GR receptor stimulation underlies impaired sensorimotor gating in CRF-overexpressing mice. CRF(1) receptors thus may play a role in the expression of psychotic features in stress-related psychiatric disorders.