Serum Corticosterone Levels In Rats Research Articles

Intranasal neuropeptide Y is most effective in some aspects of acute stress compared to melatonin, oxytocin and orexin.

Objectives: In the current study, we compared the effects of a single intranasal administration of clomipramine with effects of four neuropeptides, melatonin, oxytocin, orexin, and neuropeptide Y, to compare them in an acute stress model. Methods: The anti-stress effect was evaluated in the sucrose preference and forced swimming tests. Serum corticosterone level in rats was measured to evaluate the stress response. Results: Neuropeptide Y reduced immobilization time in the Porsolt test and decreased corticosterone levels, but increased the anhedonia. Orexin had no positive effect on animal behavior, but decreased corticosterone levels. Oxytocin decreased immobilization time, maintained anhedonia at the level of control, but did not affect corticosterone levels. Melatonin demonstrated no positive effects in any of the tests. Conclusion: The intranasal administered neuropeptide Y could be a promising compound for the treatment of stress disorders.

Flowerpot method for rapid eye movement sleep deprivation does not induce stress as defined by elevated serum corticosterone level in rats

Flowerpot method of rapid eye movement sleep (REMS) deprivation (REMSD) has been most extensively used in experiments to decipher the functions of REMS. The most common but serious criticism of this method has been presumed stress experienced by the experimental animals. The lack of systematic studies with appropriate controls to resolve this issue prompted this study. We have compared serum corticosterone levels as a marker of stress in male rats under REMSD by the flowerpot method and multiple types of control conditions. Additionally, to maintain consistency and uniformity of REMSD among groups, in the same rats, we estimated brain Na-K ATPase activity, which has been consistently reported to increase upon REMSD. The most effective method was one rat in single- or multiple-platforms set-up in a pool because it significantly increased Na-K ATPase activity without elevating serum corticosterone level. More than one rat in multiple platform set-up was ineffective and must be avoided. Also, large platform- and recovery-controls must be carried out simultaneously to rule out non-specific confounding effects.

Vendor differences in anxiety-like behaviors in female and male Sprague Dawley rats

Although Sprague Dawley outbred rats are commonly used in behavioral, physiological, and pharmacological studies, dramatic differences in responses may emerge from rats obtained from different suppliers even when sex, age, and environmental conditions are maintained constant. In the present study, we compared behavioral responses on three tests related to anxiety of Sprague Dawley female and male rats obtained from three different vendors in the United States: Charles River, Envigo, and Taconic. All rats were tested in the open field, light-dark box, and elevated zero maze. We found reduced time spent in the center area of the open field and decreased light compartment duration in the light-dark box test in female and male rats from Taconic compared to Charles River and Envigo rats, suggesting anxiety-like behaviors differ between the three vendors. No vendor differences were found on performance in the elevated zero maze. Furthermore, the contribution of stress hormones to vendor differences was examined by measuring serum corticosterone levels in rats 30 min after exposure to the elevated zero maze. There were no vendor differences in corticosterone levels, suggesting that endogenous levels of stress hormones most likely did not contribute to vendor differences in anxiety-like behaviors. Collectively, these findings highlight the importance of vendor selection of the Sprague Dawley stock for research involving behavioral tests related to anxiety.

The effects of 1-methylnaphthalene after inhalation exposure on the serum corticosterone levels in rats.

This paper reports on the trend of the stressogenic stimulus caused by a repeated exposure to 1-methylnaphthalene (1-MN) vapors at the nominal concentrations of 0 mg/m3 (the control restrainer), 50 mg/m3 or 200 mg/m3 in the nose-only inhalation system, by analyzing the serum corticosterone (CORT) levels in rats. Three groups of rats were exposed in restrainers to 1-MN vapors at the nominal concentrations of 0 mg/m3, 50 mg/m3 or 200 mg/m3 for 5 days. One control group of animals spent all the time during the experiment in an individually ventilated plastic cage. The serum CORT concentrations were determined in all 4 groups of the rats. The blood samples drawn from the tail vein were collected every day after termination of the 6-h exposure. On the fifth day, blood samples were collected 15 min, 30 min, 45 min, 1 h, and 3 h after termination of the 6-h exposure. On the fifth day of the study, no statistically significant changes in body weights between all groups of animals were found. After 5 days of the observation, increased food intake in the control groups was noted. Significantly higher CORT concentrations in the rats exposed to 1-MN at 200 mg/m3 and in the animals from the control restrainer were found, comparing to the animals exposed to 1-MN at 50 mg/m3 and the animals from the control cage. The application of 6-h restraining induced high concentrations of the stress hormone, CORT, in the blood of rats. The short-term exposure of rats to 1-MN non-linearly reduced the restraint stress measured with CORT concentration. Int J Occup Med Environ Health. 2020;33(5):691-9.

Corticosterone after acute stress prevents the delayed effects on the amygdala.

Even a single 2-hour episode of immobilization stress is known to trigger anxiety-like behavior and increase spine-density in the basolateral amygdala (BLA) of rats 10 days later. This delayed build-up of morphological and behavioral effects offers a stress-free time window of intervention after acute stress, which we used to test a protective role for glucocorticoids against stress. We observed that post-stress corticosterone, given 1 day after acute stress in drinking water, reversed enhanced anxiety-like behavior 10 days later. Quantification of spine-density on Golgi-stained BLA principal neurons showed that the same intervention also prevented the increase in spine numbers in the amygdala, at the same delayed time-point. Further, stress elevated serum corticosterone levels in rats that received vehicle in the drinking water. However, when stress was followed 24 h later by corticosterone in the drinking water, the surge in corticosterone was prevented. Together, these observations suggest that corticosterone, delivered through drinking water even 24 h after acute stress, is capable of reversing the delayed enhancing effects on BLA synaptic connectivity and anxiety-like behavior. Strikingly, although the immobilization-induced surge in corticosterone by itself has delayed detrimental effects on amygdalar structure and function, there exists a window of opportunity even after stress to mitigate its impact with a second surge of exogenously administered corticosterone. This provides a framework in the amygdala for analyzing how the initial physiological and endocrine processes triggered by traumatic stress eventually give rise to debilitating emotional symptoms, as well as the protective effects of glucocorticoids against their development.

Effect of acupuncture stimulation on rats with depression induced by water-immersion stress

Depression is a kind of mood disorder. The incidence of depressed patients has demonstrated an upward trend in recent years. Symptoms may improve with treatments such as pharmacotherapy and cognitive-behavioral therapy, but such approaches may exert strong side effects, and therapeutic effects can be slow. We studied how acupuncture stimulation would affect depression as a method to reduce side effects. Mild depression was induced in rats by 1-week water-immersion stress. We treated these mildly depressed rats with either acupuncture stimulation at the “Bai-Hui” (GV 20) and “Yintáng” (Ex-HN3) points, or antidepressants. We then measured the immobile time and serum corticosterone level in rats. Immobile time and serum corticosterone level decreased on stimulation with acupuncture or antidepressants. These findings suggest that mild depression in rats was improved by stimulation with acupuncture The mechanisms underlying such improvement may effect HPA system activated by this stress, and inhibit the response to lead to the disorder of the hippocampal nerve cell.

Effects of repeated co-treatment with fluoxetine and risperidone on the behavioural effects and serum corticosterone level in rats subjected to the forced swimming test

Effects of repeated co-treatment with fluoxetine and risperidone on the behavioural effects and serum corticosterone level in rats subjected to the forced swimming test

Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats

Repeated injections of corticosterone (CORT) induce the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depressive-like behavior. This study aimed to examine the antidepressant-like effect and the possible mechanisms of total glycosides of peony (TGP) in the CORT-induced depression model in rats. The results showed that the 3-week CORT injections induced the significant increase in serum CORT levels in rats. Repeated CORT injections also caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Moreover, it was found that brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus and frontal cortex were significantly decreased in CORT-treated rats. Treatment of the rats with TGP significantly suppressed the depression-like behavior and increased brain BDNF levels in CORT-treated rats. The results suggest that TGP produces an antidepressant-like effect in CORT-treated rats, which is possibly mediated by increasing BDNF expression in the hippocampus and frontal cortex.

Increased rat serum corticosterone suggests immunomodulation by stimulation of the vagal nerve

The role of the vagal nerve within the immune system has not been fully elucidated. Vagal afferents connect to several central nervous system structures, including the hypothalamus. We investigated the effect of vagal nerve stimulation (VNS) on serum corticosterone levels in rats. Corticosterone levels were measured following 1 h of high frequency (30 Hz) or low frequency (1 Hz) VNS in awake animals. There was a significant increase ( p < 0.05) in serum corticosterone levels following 30 Hz VNS compared to 1 Hz VNS or sham stimulation. These results suggest an immediate effect of VNS on the hypothalamic pituitary-adrenal (HPA) axis and support the role of the vagal nerve in immunomodulation.

Antidepressant-like effects of curcumin on serotonergic receptor-coupled AC-cAMP pathway in chronic unpredictable mild stress of rats

Serotonergic receptors take their physiologic effects by affecting adenylyl cyclase (AC) catalytic activity and cyclic adenosine monophosphate (cAMP) concentration. AC-cAMP second messenger pathway has been recently suggested to play an important role in depression. Therefore, the compound that regulates the signal pathway may have potential as antidepressant. Curcumin is the main component of Curcuma longa L, a well-known indigenous herb with comprehensive bioactivities. In the present study, we investigated the effects of chronic unpredictable mild stress (CUMS) and curcumin on behaviours and serotonergic receptor-coupled AC-cAMP signal pathway in rats. Curcumin produced beneficial effects on the stressed rats by effectively improving CUMS-induced low sucrose consumption and reducing serum corticosterone levels in rats. Moreover, curcumin enhanced AC activity and cAMP levels in platelet and various brain regions, and up-regulated mRNA expressions of AC subtypes AC 2, AC 8 and cAMP response element binding protein (CREB) in the hippocampus, cortex and hypothalamus of the CUMS rats. Curcumin also attenuated CUMS-induced reductions of 5-hydroxytryptamine (5-HT) levels and high expressions of central 5-HT 1A/1B/7 receptors in rats. These results suggested that the potent antidepressant property of curcumin might be attributed to its improvement of AC-cAMP pathway as well as CREB via suppressing central 5-HT 1A/1B/7 receptors in the CUMS rats. Our findings provided a basis for examining the interaction of serotonergic receptors and AC-cAMP pathway in depression and curcumin treatment.

Effect of Subcutaneous Injection and Oral Voluntary Ingestion of Buprenorphine on Post-Operative Serum Corticosterone Levels in Male Rats

Background: Adequate peri-operative analgesia may reduce post-operative stress response and improve recovery in laboratory animals. We have established a method involving repeated automated blood sampling, allowing quantification of serum corticosterone levels in rats for stress assessment without stress-inducing handling or restraint. In the present study, the effects of the commonly used route of buprenorphine administration (0.05 mg/kg injected subcutaneously) were compared with oral administration (0.4 mg/kg mixed with Nutella® and orally administered by voluntary ingestion) in male Sprague-Dawley rats. Methods: A catheter was placed in the jugular vein and attached to an Accusampler® for automated blood sampling. During 96 h after surgery, blood was collected at specified time points. Pre- and post-operative body weights and water consumption were registered. Results: Buprenorphine significantly suppressed levels of circulating corticosterone after the oral but not after the subcutaneous treatment. Both buprenorphine treatments had a positive impact on maintenance of body weight and water consumption, compared to the control group that received no buprenorphine. Conclusion: The present investigation suggests that oral voluntary ingestion ad libitum is an efficacious, convenient and non-invasive way of administering peri-operative buprenorphine to rats, as judged by corticosteroid response and effects on body weight and water consumption.

The effect of chronic food and water restriction on open-field behaviour and serum corticosterone levels in rats.

In operant conditioning experiments, two methods are commonly used to motivate laboratory rats to perform designated tasks. The first is restricting food so that rats are forced to lose 20% of body weight within one week, followed by maintenance at 80% of the baseline weight for the remainder of the experiment. The second is restricting access to water to 15 min in each 24 h period. These methods are effective in motivating the animals. There is, however, little information available on the effects on performance in tests of behaviour that are not related to operant conditioning. In addition, it is not clear if these commonly used methods of food and water restriction will lead to physiological stress as indicated by an elevation of serum corticosterone. Male rats were either food-restricted to reduce and maintain their weight at 80% of baseline weight, or were restricted to 15 min access to water every 24 h. Activity in the open field was significantly greater in food-restricted rats than in water-restricted or control rats, but freezing behaviour was similar in all experimental groups. Food-restricted rats had a higher mean serum corticosterone level than water-restricted and control rats 37 days after the start of the experimental period. These data suggested that chronically restricting food and maintenance of body weight at 80% of baseline body weight led to significant behavioural changes and physiological stress. In contrast, water restriction did not lead to changes in behaviour or corticosterone levels. A second experiment was conducted to compare the effects of food restriction to 80% of baseline body weight, as described above, with a less stringent protocol in which test rats were initially reduced to 80% of baseline weight, but were then maintained at 80% of an ad libitum fed control rat's weight. Serum corticosterone levels and adrenal gland weights were measured after the initial week of forced weight loss and after maintenance for 21 days. Forced loss of 20% of body weight in the first week led to significantly increased serum corticosterone levels and adrenal gland weights compared to ad libitum fed controls. Serum corticosterone levels and adrenal gland weights in rats maintained at 80% of their initial body weight for 21 days remained higher than ad libitum fed control rats. However, rats maintained at 80% of an ad libitum fed control rat's weight did not differ from control rats in serum corticosterone levels or adrenal gland weights at the end of the 21-day study period. Adjustment of the feeding regimen in this manner eliminated physiological evidence of chronic stress.

Adrenocortical response and regional T-lymphocyte activation patterns following minimally invasive surgery in a rat model.

Laparoscopic surgery is associated with less tissue trauma and postoperative pain as well as a more rapid recovery than open surgery. We hypothesized that these factors may result in less immune impairment following laparoscopic surgery. We measured mitogen-induced surface interleukin-2 receptor (IL2R) expression and lymphocyte proliferation in CD4+ and CD8+ T-lymphocytes as well as serum corticosterone levels in rats 24 h following open (OP) and laparoscopic (LAP) fundoplication. Serum corticosterone levels were lower in LAP vs OP rats (p = 0.02). CD4+ IL2R expression was higher in the blood, but not in the spleen, in LAP vs OP animals (p = 0.02). CD8+ IL2R expression was similar in both groups. Mitogen-induced lymphocyte proliferation was no different in the blood but decreased in the spleen in LAP vs OP rats (p = 0.03). Compared to open surgery, laparoscopic fundoplication in the rat results in lower adrenocortical hormone levels and better-preserved T-helper-cell activation in the blood. Lymphocyte proliferation is suppressed in the spleen 24 h after laparoscopic surgery. Minimally invasive surgery may better preserve cell-mediated immunity in the early postoperative period.

Repeated treatment with antidepressant drugs and/or electroconvulsive shock (ECS) does not affect the quinpirole-induced elevation of the serum corticosterone concentration in rats

The selective dopamine D2 receptor agonist quinpirole (0.03-1 mg/kg intra peritoneally) increased dose-dependently the serum corticosterone level in rats. The effect of the maximum dose of quinpirole (0.3 mg/kg intraperitoneally) was antagonized in a dose- dependent manner by the selective D2 receptor antagonist sulpiride (3-30 mg/kg intra peritoneally), but not by the selective D(1) receptor antagonist SCH-23390 (3 mg/kg intra peritoneally). Imipramine and amitriptyline (10 mg/kg per os), administered acutely or repeatedly (twice daily for 14 days), did not affect the corticosterone response to quinpirole (0.1 mg/kg intraperitoneally). The response was modified neither in animals treated repeatedly with electroconvulsive shock (ECS) (seven shocks every 2 days), nor after their combined repeated treatment with imipramine and ECS. The above results indicate that repeated treatment with antidepressant drugs and/or ECS does not affect the sensitivity of dopamine D2 receptors involved in the corticosterone response to quinpirole.

Substituted 5-amino-4,5,6,7-tetrahydroindazoles as partial ergoline structures with dopaminergic activity

Two series of tetrahydroindazoles were synthesized and evaluated for dopaminergic activity. A number of these partial ergoline analogues possess substituents that could mimic the C-8 substituent of the dopaminergic ergolines. Of the unsymmetrically substituted amine series 7a-k, the (monopropylamino)tetrahydroindazole 7b was most interesting as it was found to selectively activate the dopamine (DA) autoreceptor at a dose of 5 mg/kg in rats. The disubstituted amines 7g-k had significant DA postsynaptic activity as measured by increases of serum corticosterone levels in rats. The 6-substituted-5-aminotetrahydroindazoles 10a-d were found to possess only marginal dopaminergic activity.

In Vivo Effects of Glucocorticoids on Serum Corticosterone Levels in Rats

In vivo effects of glucocorticoids on rat serum corticosterone level were investigated by using a simple and convenient HPLC-UV detection method. Serum corticosterone level was decreased by a single injection of hydrocortisone, methylprednisolone, betamethasone, dexamethasone or fluocinonide.

Mechanism of bromocriptine-induced hyperglycaemia

Results reveal that bromocriptine at a dose of 6 mg/kg. I.P. in mice caused a significant hyperglycaemic effect which was accompanied by a marked increase in liver glycogen. After adren̂alectomy, the effect of bromocriptine on serum glucose level was reduced whereas its effect on liver glycogen content was abolished. In rats, administration of bromocriptine (17.5 mg/kg I.P.) induced a significant rise in serum glucose level which was associated with marked reduction in serum insulin activity and increase in serum corticosterone level with no effect on serum triiodothyronine (T3) or thyroxine (T4) levels. It could be concluded that bromocriptine-induced hyperglycaemia might be attributed at least partially to inhibition of insulin release and stimulation of corticosterone secretion. Previous studies disclosed that bromocri tine produced a marked hyperglycaemic effect in mice (1). This effect could be correlated with insulin secretion since bromocriptine was shown to inhibit glucose-stimulated insulin release by mouse pancreatic islets (2,3). In the present study, the effect of bromocriptine on the serum levels of insulin and corticosterone was investigated in an attempt to explain the mechanism of hyperglycaemia caused by bromocriptine. Our results indicate that bromocriptine-induced hyperglycaemia was accompanied by a significant inhibition of serum insulin level and marked elevation in serum corticosterone level in rats. The hyperglycaemic effect was reduced by adrenalectomy.

Glucocorticoid independent mediation of interleukin-1 induced changes in serum zinc and liver metallothionein levels

Interleukin-1 (IL-1) causes changes in zinc metabolism which have been attributed to mediation, at least in part, by glucocorticoids. However, IL-1 was found to actually lower serum corticosterone levels in rats. In addition, adrenalectomy only partially inhibited the ability of IL-1 to depress serum zinc levels and increase the amount of zinc associated with hepatic metallothionein. Furthermore, IL-1 increased total liver metallothionein protein to similar levels in both adrenalectomized and normal rats. Administering the synthetic glucocorticoid dexamethasone with IL-1 to adrenalectomized rats produced additive, but not synergistic effects on serum zinc and metallothionein concentrations. Studies with actinomycin D suggested that IL-1 induction of metallothionein might involve glucagon.

Effect of intracerebroventricular clonidine on serum corticosterone levels in rats.

In conscious, nonstressed rats clonidine given intracerebroventricularly (i.c.v.) increased the pituitary-adrenocortical response evaluated indirectly from corticosterone concentration. The maximum significant increase occurred 60 min after a dose of 10 micrograms. The alpha 2-adrenoceptor antagonist yohimbine given alone i.c.v. in low doses (0.05-1 microgram) had no effect on plasma corticosterone levels, but at higher doses (5 and 10 micrograms) it produced a significant rise in these levels. Phenoxybenzamine (0.05-10 micrograms, i.c.v.) caused a dose-related increase in corticosterone secretion. Pretreatment of rats with yohimbine considerably antagonized (up to 70%) the increase of corticosterone response induced by clonidine. Phenoxybenzamine failed to alter this effect. The depletion of brain catecholamines by alpha-methyl-p-tyrosine caused an increase in serum corticosterone concentration. The rise was suppressed by clonidine (10 micrograms, i.c.v.), and this suppression was antagonized in part by pretreatment with yohimbine. These data support the concept of the noradrenergic inhibition of ACTH secretion in rats. It seems likely that clonidine injected i.c.v. induces stimulation of corticosterone through the activation of presynaptic alpha 2-adrenoceptors and inhibition of noradrenaline release. The clonidine-induced inhibition of corticosterone after alpha-methyl-p-tyrosine seems to be mediated by alpha-adrenoceptors located postsynaptically.

The involvement of central histamine receptors in stress-induced responses of serum corticosterone and free fatty acids and in gastric ulcer development.

Mild stress of restraint for 10 min at an ambient temperature of 18 degrees C increased serum corticosterone levels in rats considerably. Histamine given intravenously prior to restraint alone significantly further intensified the stress-induced elevation of serum corticosterone. Dimaprit and cimetidine failed to modify corticosterone responses to the mild stress. Severe stress of restraint and cold of 3 h duration increased serum corticosterone and free fatty acid levels considerably. Histamine given prior to stress exposure left the corticosterone and hyperlipaemic responses to severe stress unchanged. Dimaprit inhibited and cimetidine intensified the stress-induced hyperlipaemia. The most striking finding in the present experiment was a powerful inhibition of gastric stress ulcer generation by intraventricularly administered histamine. Dimaprit was similarly effective. This strong anti-ulcer effect of histamine was abolished by intraventricular pretreatment of rats with either H1- or H2-receptor antagonists, chloropyramine or cimetidine. The results may suggest that in the rat a mild stress does not fully activate central histaminergic pathways involved in corticosterone responses. During severe stress histamine considerably prevents gastric ulcer generation and both H1- and H2-receptors mediate this action of histamine.