Changes In Corticosterone Concentrations Research Articles

The effects of daily mitotane or diazepam treatment on the formation of chronic stress symptoms in newly captured wild house sparrows.

Wild animals brought into captivity frequently experience chronic stress and typically need a period of time to adjust to the conditions of captivity (restraint, artificial lighting, altered diet, human presence, etc.), to which they may never fully acclimate. Changes in mass, the hypothalamic-pituitary-adrenal axis and heart rate parameters have been observed over the first week in newly captive house sparrows (Passer domesticus). In this study, we tested the effects of two drugs, diazepam and mitotane, in preventing the chronic stress symptoms caused by captivity, compared with oil-injected control animals. Diazepam is an anxiolytic that is widely prescribed in humans and other animals and has been shown in some cases to reduce physiological stress. Mitotane is an agent that causes chemical adrenalectomy, reducing the body's capacity to produce glucocorticoid hormones. Our mitotane treatment did not cause the expected change in corticosterone concentrations. Baseline corticosterone was higher after a week in captivity regardless of the treatment group, while stress-induced corticosterone did not significantly increase above baseline after a week in captivity in any treatment group. However, mitotane treatment did have some physiological effects, as it reduced the resting heart rate and the duration of the heart rate response to a sudden noise. It also prevented the increase in nighttime activity that we observed in control animals. There was no effect of diazepam on corticosterone, resting heart rate, activity or heart rate response to a sudden noise, and no effect of either treatment on the sympathetic vs parasympathetic control of the resting heart rate. Together, these data suggest that mitotane, but not diazepam, can have a modest impact on helping house sparrows adapt to captive conditions. Easing the transition to captivity will likely make conservation efforts, such as initiating captive breeding programs, more successful.

Changes in corticosterone concentrations and behavior during Mycoplasma gallisepticum infection in house finches (Haemorhous mexicanus)

Glucocorticoid stress hormones are important for energy mobilization as well as regulation of the immune system, and thus these hormones are particularly likely to both influence and respond to pathogen infection in vertebrates. In this study, we examined how the glucocorticoid stress response in house finches (Haemorhous mexicanus) interacts with experimental infection of the naturally-occurring bacterial pathogen, Mycoplasma gallisepticum (MG). We also investigated whether infection-induced concentrations of corticosterone (CORT), the primary glucocorticoid in birds, were associated with the expression of sickness behavior, the lethargy typically observed in vertebrates early in infection. We found that experimental infection with MG resulted in significantly higher CORT levels on day 5 post-infection, but this effect appeared to be limited to female house finches only. Regardless of sex, infected individuals with greater disease severity had the highest CORT concentrations on day 5 post-infection. House finches exposed to MG exhibited behavioral changes, with infected birds having significantly lower activity levels than sham-inoculated individuals. However, CORT concentrations and the extent of sickness behaviors exhibited among infected birds were not associated. Finally, pre-infection CORT concentrations were associated with reduced inflammation and pathogen load in inoculated males, but not females. Our results suggest that the house finch glucocorticoid stress response may both influence and respond to MG infection in sex-specific ways, but because we had a relatively low sample size of males, future work should confirm these patterns. Finally, manipulative experiments should be performed to test whether the glucocorticoid stress response acts as a brake on the inflammatory response associated with MG infection in house finches.

Effects of different blood collection methods on indicators of welfare in mice.

Blood collection is a common experimental procedure for which there are many different methods, each with its own advantages and disadvantages. Researchers should use methods that minimize pain, suffering, distress and lasting harm to animals while meeting study requirements. The authors evaluated stress, activity and tissue damage in BALB/cO1aHsd mice after collecting blood using one of six methods: retrobulbar bleeding with thin or thick capillaries, tail vein bleeding, saphenous vein bleeding, facial vein bleeding or jugular vein bleeding. The authors compared in-cage activity, corticosterone concentration and performance in open-field tests between treatment groups and collected histologic samples at 1 h, 3 d and 14 d after bleeding. Mice that underwent retrobulbar bleeding with a thick capillary had a smaller change in corticosterone concentration and higher in-cage activity immediately after blood collection, whereas mice that underwent jugular vein bleeding had a greater change in corticosterone concentration and lower in-cage activity and open-field activity. Mice that underwent saphenous vein bleeding had a high incidence of histological change at 1 h, 3 d and 14 d after blood collection, but few indicators of histological change were present in other groups at 14 d after blood collection. These results suggest that, when collecting a small volume of blood, retrobulbar bleeding with a thick capillary and without anesthesia causes the least stress in mice, whereas jugular vein bleeding and facial vein bleeding cause the most stress and saphenous vein bleeding causes the most lasting damage in mice.

Bovine serum albumin as the dominant form of dietary protein reduces subcutaneous fat mass, plasma leptin and plasma corticosterone in high fat-fed C57/BL6J mice.

Increasing evidence suggests that the source of dietary protein can have an impact on weight gain and fat mass during high-fat feeding in both humans and rodents. The present study examined whether dietary bovine serum albumin (BSA) as the dominant source of protein alters energy balance and adiposity associated with high-fat feeding. C57/BL6J mice were given a diet with 10 % of energy from fat and 20 % of energy from casein or a diet with 45 % of energy from fat and either 20 % of energy from casein (HFD) or BSA (HFD+BSA) for 13 weeks. The HFD+BSA diet did not significantly alter daily energy expenditure, locomotor activity and RER, but did increase cumulative energy intake and percentage of lean mass while reducing feed efficiency and percentage of fat mass when compared with the HFD (P< 0·05). In subcutaneous adipose tissue (SAT), the HFD+BSA diet increased the mRNA levels of PPARα (PPARA), carnitine palmitoyltransferase 1b (CPT1b) and uncoupling protein 3 (UCP3), but reduced the mRNA level of leptin when compared with the HFD (P< 0·05). The SAT mRNA levels of PPARA, CPT1b and UCP3 were negatively correlated (P< 0·05) with SAT mass, which was reduced in HFD+BSA mice compared with HFD controls (P< 0·01). No differences in epididymal fat mass existed between the groups. The HFD+BSA diet normalised plasma leptin and corticosterone levels compared with the HFD (P< 0·05). While differences in leptin levels were associated with the percentage of fat mass (P< 0·01), changes in corticosterone concentrations were independent of the percentage of fat mass (P< 0·05). The data suggest that the HFD+BSA diet influences plasma leptin levels via SAT mass reduction where mRNA levels of genes linked to β-oxidation were increased, whereas differences in plasma corticosterone levels were not related to fat mass reduction.

Relationship between plasma and tissue corticosterone in laying hens (Gallus gallus domesticus): implications for stress physiology and animal welfare

This study directly compared the dynamics of change in plasma corticosterone concentration with the dynamics of change in tissue corticosterone concentration in laying hens. In concert, we measured the rate of gluconeogenesis, glycogenesis, and glycolysis in the liver, kidney, skeletal muscle, and heart. We evaluated these changes acutely, over 3 h in response to an adrenocorticotropic hormone (ACTH) injection, and chronically, over 24 h in response to food and water deprivation. In response to ACTH injection, there was a significant (P < 0.05) increase in plasma corticosterone concentration and a parallel significant increase in corticosterone concentration in the skeletal muscle, kidney, and heart. However, the change in corticosterone concentration in the liver did not parallel the plasma, at times it was greater than the plasma, and there was a second significant increase (P < 0.05) in corticosterone concentration in the liver after 180 min. Under these conditions, the rate of gluconeogenesis in the liver decreased and the rate of glycogenesis increased. In contrast, after 12 h and 24 h of food and water deprivation plasma corticosterone concentration was increased, and this was paralleled by increased corticosterone concentration in the liver, an increase in the rate of gluconeogenesis and a decrease in the rate of glycogenesis. After ACTH injection, glucose concentration in the liver was not significantly depleted but after 12 h or 24 h of food and water deprivation it was significantly depleted (P < 0.05). Plasma corticosterone concentration provided different insight into the effect of the stressor on hen physiology under acute and chronic conditions. Our data suggest that extending our evaluation of stress to the site of corticosterone action, that is, the target tissue, may enhance our ability to evaluate stress and the welfare of laying hens.

Prenatal exposure to noise stress: anxiety, impaired spatial memory, and deteriorated hippocampal plasticity in postnatal life.

Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals, this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2, and 4 hour(s). The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison with the nonpregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals.

Wound healing reduces stress-induced immune changes: evidence for immune prioritization in the side-blotched lizard.

Immune system function is affected by a variety of exogenous and endogenous stressors. Most studies have focused on the effect of stressors on immune function, but not necessarily on trade-offs within the immune system and interactions with energy-mobilizing hormones. In this study, we examined how bactericidal ability and corticosterone interacted by applying acute restraint stress in a non-model organism, the side-blotched lizard (Uta stansburiana), 10 days after receiving a cutaneous wound. We found a decrease in bactericidal ability in wounded animals after restraint stress. However, the percentage healed during the first 7 days was positively correlated with bactericidal ability 10 days after wounding. In addition, the magnitude of change in corticosterone concentration during the acute stress was positively correlated with the percentage of wound healing during the first 3 days. These two relationships may demonstrate a "faster is better" strategy. If energy is invested heavily in the initial wound healing stages, the individual may be able to mount a more effective immune and stress response earlier.

REDD1 (regulated in development and DNA damage response 1) expression in skeletal muscle as a surrogate biomarker of the efficiency of glucocorticoid receptor blockade

Glucocorticoids are potent regulators of cell metabolism, and in part act through a receptor-based mechanism to alter the transcription of target genes. A plethora of studies have utilized the glucocorticoid receptor antagonist, RU-486, both in vivo and in vitro, to reverse or prevent hormone-induced alterations in gene transcription. However, although RU-486 potently blocks many of the functions of the receptor, it does not lower plasma concentrations of the hormone, and a biomarker for the effectiveness of RU-486 in blocking receptor activation is lacking. In the present study, we demonstrate glucocorticoid-induced changes in expression of a protein referred to as regulated in development and DNA damage response (REDD1) in a variety of mouse models of hypercortisolemia including stroke, type 2 diabetes, and stress induced by confinement. Notably REDD1 expression in skeletal muscle positively correlated with changes in corticosterone concentrations in all conditions. RU-486 had no effect on corticosterone concentrations, but strongly attenuated the stroke-, diabetes-, and stress-induced changes in REDD1 expression. Overall, the results of the present study suggest that changes in REDD1 expression in skeletal muscle represent an excellent surrogate biomarker for the efficacy of RU-486 treatment in repressing glucocorticoid action.

Early and Delayed Effects of Hypoxia during the Infantile Period on Behavioral and Hormonal Reactions of Rats

We studied the early and delayed effects of hypoxia during the infantile period on the behavioral reactions and corticosterone concentration in male rats. The elevation of corticosterone concentration, decrease in the immobility time (forced swimming test), and increase in the nociceptive response (formalin test) were observed in 7-day-old rats immediately after hypoxia. Adult animals exposed to hypoxia at the age of 7 days exhibited elevated basal corticosterone level and lengthened immobility time. Hypoxia had the same effect on plasma corticosterone concentration in 7-day-old and adult rats. Changes in corticosterone concentration after forced swimming were shown to differ in hypoxic animals and non-hypoxic specimens. Studying the dynamics of age-related variations in the test parameters will contribute to the understanding of pathogenetic mechanisms and development of new methods for pharmacological correction of postnatal changes in CNS after hypoxia during early ontogeny.

Adrenocortical function of Arctic-breeding glaucous gulls in relation to persistent organic pollutants

Unpredictable changes in the environment stimulate the avian hypothalamo–pituitary–adrenal axis to produce corticosterone, which induces behavioural and metabolic changes that enhance survival in the face of adverse environmental conditions. In addition to profound environmental perturbations, such as severe weather conditions and unpredictable food shortages, many Arctic-breeding birds are also confronted with chronic exposure to persistent organic pollutants (POPs), some of which are known to disrupt endocrine processes. This study investigated the adrenocortical function of a top predator in the Arctic marine environment, the glaucous gull ( Larus hyperboreus). High concentrations of organochlorines, brominated flame retardants and metabolically-derived products in blood plasma of incubating glaucous gulls were associated with high baseline corticosterone concentrations in both sexes and a reduced stress response in males. Contaminant-related changes in corticosterone concentration occurred over and above differences in body condition and seasonal variation. Chronically high corticosterone concentrations and/or a compromised adrenocortical response to stress can have negative effects on the health of an individual. The results of the present study suggest that exposure to POPs may increase the vulnerability of glaucous gulls to environmental stressors and thus could potentially compromise their ability to adapt to the rapidly changing environmental conditions associated with climate change that are currently seen in the Arctic.

A comparative study to the effect of tianeptine and fluoxetine on open-field behaviour and serum corticosterone concentration

Objective To compare the effect of tianeptine and fluoxetine on behaviour and serum corticosterone concentration changes induced by stress and its antidepression mechanism. Methods 33 rats were randomly allocated into control(n ＝6), 4 week-stress with saline(n ＝6), 4 week-stress with tianeptine(n ＝6)and 4 week-stress with fluoxetine (n ＝15) groups.Forced swimming test was used to set up stress animal model,and open-field test was used to assess the behavior,then concentration of serum corticosterone was detected by enzyme-linked immunosorbent assays(ELIA). Results The number of crossing and standing up of 4 week-stress with fluoxetine group[(73.53±43.66),(10.00±11.14)] were much higher than 4 week-stress with saline group[(7.67±3.01),P ＜0.01;(0.67±0.82),P ＜0.05],while no difference was found compared with control group and 4 week-stress with tianeptine group; the number of stool of 4 week-stress with fluoxetine [(3.40±2.47),P ＜0.01]and 4 week-stress with saline group[(3.17±3.19),P ＜0.05] were much lower than control group(7.00±1.79), while no difference was found compared with 4 week-stress with tianeptine group(4.67±2.34). Concentration of serum corticosterone of control group[(191.60±116.41)ng/ml] and 4 week-stress with fluoxetine group[(315.49±146.35)ng/ml] were both much lower than 4 week-stress with saline group[(765.37±250.87)ng/ml,P ＜0.01] and 4 week-stress with tianeptine group[(863.49±282.31)ng/ml,P ＜0.01].There was no difference when compared with the concentration of serum corticosterone of control group and 4 week-stress with fluoxetine group, while no difference was found when compared with 4 week-stress with saline group and 4 week-stress with tianeptine group. Conclusions Both tianeptine and fluoxetine can reverse stress-induced behavior changes, and the fluoxetine is even better to improve the depression induced by stress;meanwhile the effect of reverse the level of serum corticosterone concentration of fluoxetine is much higher than tianeptine. Key words: Stress; Corticosterone; Behavior; Tianeptine; Fluoxetine

Initial transference of wild birds to captivity alters stress physiology

Maintaining wild animals in captivity has long been used for conservation and research. While often suggested that captivity causes chronic stress, impacts on the underlying stress physiology are poorly understood. We used wild-caught chukar (Alectoris chukar) as a model avian species to assess how the initial 10 days of captivity alters the corticosterone (CORT) secretory pathway. In the first few days of captivity, birds lost weight, had lower hematocrit and demonstrated changes in CORT concentrations. Both baseline and restraint-stress-induced CORT concentrations decreased by days 3–5 of captivity and remained significantly lower throughout the 10 days although stress-induced concentrations began to recover by day 9. To delineate potential mechanisms underlying these CORT changes, we evaluated alterations to the hypothalamic–pituitary–adrenal (HPA) axis. Although chukar appear to be resistant to arginine vasotocin’s (AVT) effects on CORT release, adrenocorticotropin hormone (ACTH) stimulated CORT release; however, ACTH stimulation did not differ during the 10 days of captivity. In contrast, negative feedback axis sensitivity, as determined by both dexamethasone suppression as well as endogenous negative feedback, decreased by day 5 but was regained by day 9. In addition, the combined stressors of capture and long distance transport eliminated the animals’ ability to mount an acute CORT response on the day following the move. Therefore, introduction into captivity appeared to shift the chukar into a temporary state of chronic stress that began to recover within 9 days. The duration of these alterations likely varies due to differences in capture techniques, transport distance, and species studied.

Circadian changes in serum corticosterone levels affect hearing in mice exposed to noise

We assessed the relationship between changes in corticosterone concentrations and hearing in mice exposed to noise during the light (inactive) and dark (active) phases. Serum corticosterone concentrations and hearing levels were measured before, and 1, 3, 5, 7, and 10 days after, noise exposure between 8:00-11:00 h and 15:00-18:00 h. Serum corticosterone concentrations were significantly lower at 8:00-11:00 h than at 15:00-18:00 h and were significantly lower before than after noise exposure. In addition, serum corticosterone concentrations were significantly lower at 11:00 h after noise exposure than at 18:00 h before noise exposure. Mice exposed to noise at 8:00-11:00 h showed significantly elevated threshold shifts after noise exposure than did mice exposed to noise at 15:00-18:00 h. Endogenous serum corticosterone concentration has a significant effect on hearing after noise exposure. Noise exposure during the inactive phase of the hypothalamic-pituitary-adrenal axis may be more harmful to the auditory system than noise exposure during the active phase of the hypothalamic-pituitary-adrenal axis.

Odour learning and immunity costs in mice

There is accumulating evidence that learning is metabolically costly. One way in which this may manifest itself is in trade-offs between learning effort and immune function, with learning increasing susceptibility to infection. We tested this idea in the context of odour learning using outbred (BKW) male laboratory mice. Mice were exposed to three experimental treatments in which they were required to learn different numbers of urinary odours. While treatment affected the extent to which mice habituated to test odours during training, differences were not a simple function of the number of odours. The fact that there was also no significant effect of treatment on the degree of preference for novel over familiar odours in subsequent tests suggests mice retained learned odour profiles equally well regardless of the number of odours. That subsequent infection with Babesia microti increased with the number of odours mice had to learn is then consistent with an increased cost to learning effort when more odours were presented. Analysis within treatments, and relationships with the change in corticosterone concentration over the period of the experiment, suggested that it was a failure to learn, rather than maintaining learning performance, in more difficult learning tasks that led to greater infection. As in a previous study of maze learning in the strain, there was no direct relationship between infection and measures of peripheral antibody (total IgG) titre. The results are discussed in relation to studies in other learning contexts and reported relationships between glucocorticoid hormones and learning outcomes.

The role of circadian rhythm on the pharmacokinetic of methotrexate in streptozotocin-induced diabetes mellitus rats

Chronopharmacokinetic studies have been conducted both in animals and humans. Anticancer agents are of great interest due to their narrow therapeutic range and large pharmacokinetic variability. It was reported that the pharmacokinetics of MTX showed a circadian rhythm in rats and humans. Since diabetes-induced physiological changes can affect pharmacokinetics of drugs, it was reported that MTX blood concentration in diabetic rats was higher than that of the control groups. The present study was designed to elucidate whether these diabetes-induced changes in pharmacokinetics occurred during the day and thus administered MTX at four different times in streptozotocin-induced diabetes mellitus (SIDM) rats. Blood samples were drawn at 5, 15, 30, and 60 min after IV infusion of MTX in both the SIDM and control groups. Control and SIDM Area under the concentration – time curve (AUC) values showed a significant circadian rhythm with a peak located in mid-dark phase at 14:00. Clearance values were significantly low at 14:00 in the diabetic group when compared to other periods and the control group. The MTX AUC was increased when treatment with dexamethasone was given to suppress the endogenous production of corticosterone in both control and SIDM rats. These results suggest that the extent of MTX pharmacokinetics varies with the time of day in the SIDM rats and these variations might be related to changes in corticosterone concentrations.

Stress responses and disease in three wintering house finch ( Carpodacus mexicanus) populations along a latitudinal gradient

In laboratory studies, stress hormones have been shown to impair immune functions, and increase susceptibility to diseases. However, the interactions between stress hormones and disease have rarely been studied in free-ranging populations. In this study, we measured concentrations of the avian stress hormone corticosterone across four winter months (December–March) over two years in three eastern North American house finch populations ( Carpodacus mexicanus) along a latitudinal gradient. Because Mycoplasma gallisepticum infections appear in these populations in late winter, we hypothesized that the timing of the disease outbreaks could be mediated by changes in corticosterone concentrations. We found a significant increase in baseline and stress-induced plasma corticosterone concentrations in house finches without Mycoplasma symptoms in late winter; when the prevalence of Mycoplasma infection peaks. We also found that house finches with Mycoplasma symptoms had elevated stress-induced corticosterone concentrations. High baseline concentrations were associated with a low body condition and a high fat load. We found that the relationship between corticosterone concentrations and the latitude of the study population changed between years. The first year, corticosterone concentrations were lowest in the southern latitude, but became higher in the second year when average winter temperatures were low. A causal understanding of the implications for this variation in corticosterone concentrations for Mycoplasma disease dynamics awaits further studies.

Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone

Previously, we showed that corticosterone regulates BDNF mRNA levels in the hippocampus. In the present study, we have investigated the time course and dose-dependency of this effect at both the mRNA and the protein level. Corticosterone was administered in doses of 30 and 1000 μg/kg b.w. subcutaneously to adrenalectomized animals. At 3, 6, 12 and 24 h after administration BDNF and trkB mRNA levels in hippocampal subfields were measured by in situ hybridization. Our results show a dose-dependent decrease in BDNF mRNA in dentate gyrus and CA1 at 3 h. After the high dose, this decrease was 70% and 40% respectively. In addition, ELISA was performed to study if this downregulation is also detectable at the protein level. Hippocampal tissue was used from adrenalectomized animals which had received 1000 μg/kg b.w. corticosterone 4 and 6 h before decapitation. At both time points, a decrease in BDNF protein was observed; 17% at 4 h and 14% at 6 h after corticosterone, as compared to the vehicle injected controls. TrkB mRNA levels were not affected by corticosterone. However, between 6 and 24 h after treatment, increases in trkB mRNA were observed. In conclusion, we have found a transient, dose-dependent decrease in BDNF mRNA and protein in the hippocampus, which may underly changes in neuronal plasticity in the hippocampus after short-term changes in corticosterone concentrations.

Social behaviour and susceptibility to infection in house mice (Mus musculus): effects of group size, aggressive behaviour and status-related hormonal responses prior to infection on resistance toBabesia microti

Associations between social rank, immunodepression and resistance to Babesia microti infection within single-sex groups of male house mice suggest rank-dependent suites of response involving different hormonal and immune changes in relation to aggressive behaviour and group size prior to infection. Reduced resistance among high-ranking males was associated with increased serum testosterone and corticosterone concentration and reduced serum immunoglobulin, but was independent of group size. Among low-ranking males, hormonal changes were not associated with resistance to B. microti but changes in corticosterone concentration and measures of immunodepression increased with group size and aggressive behaviour. The results concur with earlier findings suggesting differences between high- and low-ranking mice in their physiological responses to social experience and consequently reduced resistance to B. microti infection among high-ranking individuals.

Interleukin 1 stimulation of the hypothalamic-pituitary-adrenal axis

The effect of varying doses of purified human interleukin 1 (IL-1) on rectal temperature (Tr), hypothalamic corticotropin-releasing hormone (CRH), pituitary and plasma adrenocorticotropic hormone (ACTH), and plamsa corticosterone was examined in intact male rats at 24 degrees C; plasma ACTH and corticosterone responses were also studied in hypophysectomized rats. In addition, IL-1-induced changes in corticosterone concentration were investigated by means of adrenal organ cultures. Tr was measured with thermocouples. CRH and ACTH levels were determined by radioimmunoassay, and corticosterone by protein-binding assay. Intravenous administration of IL-1 (0.063-1.0 ng) resulted in hyperthermia, which began 20 min postinjection and continued for an additional 30 min. IL-1 at a dose of 0.5 ng resulted in no change in hypothalamic CRH, pituitary ACTH, or plasma ACTH levels compared with saline-treated rats. Plasma corticosterone was significantly (P less than 0.05) elevated 30 min after IL-1 administration and returned to control levels after 1 h. The higher dose of IL-1 (1.0 ng) did not affect hypothalamic CRH content, but pituitary ACTH began to rise at 15 min and was significantly (P less than 0.05) elevated 30 min after injection. Rats receiving this dose displayed elevated (P less than 0.05) plasma ACTH and corticosterone levels 30 and 60 min postinjection. No change in plasma corticosterone was observed in hypophysectomized rats administered either 1 ng of IL-1 or 1 microgram of recombinant IL-1 beta (rIL-1 beta); adrenal organ cultures treated with IL-1 (10(-11) M) responded similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential plasma corticosterone responses to hippocampal stimulation.

The effect of limbic forebrain stimulation on pituitary-adrenal function was assessed by evaluating plasma corticosterone obtained prior to and following sham or electrical stimulation of urethane (1.20 g/kg) anesthetized female rats. Cortical electroencephalogram (EEG), electrocardiogram (ECG), heart rate (HR), mean arterial blood pressure (MAP), and respiration were routinely monitored. Timed blood samples (0.25 ml) were obtained from a catheterized femoral artery. The HR (Bts/min), MAP (mm of Hg), and corticosterone levels (microgram/dl) for 7 non-stimulated rats averaged over 6 sampling periods were 385 +/- 19,95 +/- 6, and 70.3 +/- 5.8 respectively. In electrically or sham stimulated rats, blood samples were taken just prior to stimulation (biphasic square waves, 100 microA, 50 or 60 Hz, 1 ms, 1 s on/1 s off for 15 or 30 min) and 5, 10, 15, and 30 min after initiation of stimulation. Significant changes in plasma corticosterone levels were obtained following stimulation of hippocampal and amygdaloid areas. In contrast, no change in corticosterone concentration was observed following stimulation of cortex, corpus callosum, fornix and a variety of other CNS areas. Detailed analysis of hippocampal influence on urethane stimulated plasma corticosterone levels showed increased plasma corticosterone levels following stimulation of CA1. In contrast, stimulation of CA3, dentate (includes CA4) and the subiculum produced significant decreases in plasma corticosterone levels. No change in corticosterone levels was observed following sham stimulation. Collectively, these data indicate that consideration must be given to the possibility that differential neuroendocrine regulatory mechanisms reside within various limbic forebrain complexes and that electrical stimulation of limbic forebrain sites of urethane anesthetized rats may provide information regarding sites inhibitory to pituitary-adrenal activity.