High Plasma Levels Of Corticosterone Research Articles

Ecophysiological responses of Liolaemus arambarensis juveniles to experimental temperature variations

Climate change increasingly influences the loss of biodiversity, especially in ectothermic organisms, which depend on environmental temperatures to obtain heat and regulate their life cycle. Studies that aim to understand the impact of temperature variation are important to better understand the possible impacts generated on the homeostasis of ectothermic organisms. Our objective was to characterize the responses of juvenile Liolaemus arambarensis lizards to abrupt changes in temperature, quantifying markers of body condition, intermediary and hormonal metabolism and oxidative balance. We collected 45 juvenile individuals of L. arambarensis (winter: 20 and summer: 25) in Barra do Ribeiro, Brazil. We transported the animals to the laboratory, where they were acclimatized for five days at a temperature of 20 °C, then divided and exposed to temperatures of 10 °C, 20 °C, 30 °C and 40 °C for 24 h. After exposure, the animals were euthanized and the brain, caudal muscle, thigh, and liver tissues were extracted for quantification of biomarkers of metabolism (glycogen and total proteins) and oxidative balance (acetylcholinesterase, superoxide dismutase, catalase, glutathione-S-transferase and lipoperoxidation) and plasma for corticosterone quantification. The results show that L. arambarensis is susceptible to sudden temperature variations, where higher temperatures caused greater activity of antioxidant enzymes, increased lipoperoxidation and higher plasma levels of corticosterone in animals eliminated in winter. The present study demonstrated that abrupt changes in temperature could significantly modify the homeostatic mechanisms of animals, which could lead to oxidative stress and a potential trade-off between survival and growth/reproduction. In this context, the organism mobilizes energy resources for survival, with possible damage to growth and reproduction. Demonstrate that a change in temperature can be a potential factor in extinction for a species given the profile of global climate change.

Corticosterone does not change open elevated plus maze-induced antinociception in mice

It has been demonstrated that the exposure of rodents to the standard elevated plus-maze (sEPM: 2 open and 2 enclosed arms) elicits defensive behavioral reactions and antinociception and also activates the hypothalamo-pituitary-adrenal (HPA) axis. We have recently reported that EPM-induced antinociception is particularly observed when rats and mice are exposed to a totally open EPM (oEPM: 4 open arms). Given that the oEPM seems to be a more aversive situation than the sEPM, we hypothesized that oEPM exposure would induce higher plasma levels of corticosterone than sEPM exposure in mice. In this study, we investigated the influence of exposure to eEPM (enclosed EPM: 4 enclosed arms), sEPM or oEPM on plasma corticosterone levels in mice, with or without prior nociceptive stimulation (2.5% formalin injection into the right hind paw). We also tested whether the nociceptive response in the formalin test and oEPM-induced antinociception are altered by adrenalectomy. Results showed that oEPM-exposed mice spent less time licking the injected paw than sEPM- and eEPM-exposed animals. All three types of EPM exposure increased plasma corticosterone when compared to the basal group, but sEPM- and oEPM-exposed mice showed higher corticosterone levels than eEPM-exposed mice. Prior nociceptive stimulation (formalin injection) did not enhance the plasma corticosterone response induced by the three types of EPM exposure. Indeed, formalin injection appeared to provoke a ceiling effect on plasma corticosterone concentration. Furthermore, neither the nociceptive response in the formalin test nor oEPM-induced antinociception was changed by adrenalectomy. Present results suggest that oEPM antinociception does not depend on corticosterone release in mice.

Effects of testosterone and corticosterone on immunocompetence in the zebra finch

The original immunocompetence handicap hypothesis (ICHH) suggested that testosterone has a handicapping effect in males by both promoting the development of sexual signals and suppressing immune function. A modified version, the stress-linked ICHH, has recently proposed that testosterone is immunosuppressive indirectly by increasing production of corticosterone. To test both the original and stress-mediated versions of the ICHH, we implanted male zebra finches taken from lines selected for divergent maximum stress-induced levels of corticosterone (high, low and control) with either empty or testosterone-filled implants. Their humoral and cell-mediated immune responses were then assessed by challenge with diphtheria:tetanus vaccine and phytohemagglutinin respectively. We found no effect of the hormone manipulations on either PHA or tetanus antibody responses, but found a significant interaction between titers of both testosterone and corticosterone on diphtheria secondary antibody response; antibody response was greatest in individuals with high levels of both hormones. There was also a significant interactive effect between testosterone treatment group and corticosterone titer on body mass; the body mass of males in the elevated testosterone treatment group decreased with increasing corticosterone titer. These results suggest that, contrary to the assumption of the stress-mediated version of the ICHH, high plasma levels of corticosterone are not immunosuppressive, but are in fact immuno-enhancing in the presence of high levels of plasma testosterone. Equally, the central assumption of the ICHH that testosterone is obligately immunosuppressive is also not supported. The same individuals with the highest levels of both hormones and consequently the most robust antibody response also possessed the lowest body mass.

Two Different Putative Genetic Animal Models of Childhood Depression

In an attempt to model childhood depression, we examined whether existing genetic animal models of depression in adult rats are also valid in prepubertal rats. Two different "depressed" rat lines were studied: the Flinders Sensitive Line (FSL) and their controls, Sprague-Dawley (SD); and the Wistar Kyoto (WKY) line and their controls, Wistar. We hypothesized that male prepubertal FSL and WKY rats would show increased swim test immobility and different patterns of social play and of basal plasma levels of corticosterone and adrenocorticotropic hormone (ACTH) compared with control rats. Prepubertal FSL and WKY rats exhibited significantly longer duration of immobility than control rats in the swim test. The FSL rats demonstrated significantly higher levels of social play behaviors and lower levels of corticosterone and ACTH compared with SD control rats, whereas WKY rats demonstrated significantly lower levels of social play behaviors and higher plasma levels of corticosterone and ACTH compared with Wistar control rats. The results might suggest that prepubertal FSL and WKY rats are both putative genetic animal models of childhood depression, exhibiting separate patterns and symptoms of childhood depression.

Vendor differences in cocaine-induced behavioral activity and hormonal interactions in ovariectomized Fischer rats

Contradictory effects of ovarian hormone on cocaine-induced behaviors have been reported in ovariectomized Fischer rats [1,2]. To determine if these discrepancies are based on where the rats were purchased, Charles River Laboratories and Taconic Fischer rats were randomly assigned to either cocaine (15 mg/kg, intraperitoneal) or saline treatment; and one of four hormone-pretreatment subgroups: vehicle, estrogen, progesterone or estrogen + progesterone. Vendor differences were observed in cocaine-induced locomotor activities; overall, Taconic rats demonstrated less locomotor activity than Charles River rats. Furthermore, vendor differences in ambulatory activity were also observed after steroid replacement treatment. In Charles River rats, estrogen + progesterone co-administration suppressed cocaine-induced increases in ambulatory activity when compared to other hormone-treated groups given cocaine. In contrast, Taconic rats showed an increase in ambulations after this drug/hormone treatment. Vendor differences were also observed in steroid effects on cocaine-induced rearing activity, where estrogen + progesterone and cocaine caused an increase in rearing in Charles River rats, but not in Taconic rats. No differences between the vendors were observed in saline- or cocaine-treated animals’ stereotypic activity. Vendor differences in cocaine-induced locomotor activity were not due to differences in cocaine metabolism, as no differences in plasma levels of benzoylecgonine were observed. Interestingly, Taconic animals had overall higher plasma levels of corticosterone than Charles River rats. Thus, intrinsic differences between different lines of Fischer rats may affect the outcome of ovarian hormone interactions in cocaine-induced behavioral alterations.

The Effects of an “El Niño” Southern Oscillation Event on Reproduction in Male and Female Blue-Footed Boobies,Sula nebouxii

This study attempted to determine endocrine correlates of reproductive success in relation to major deleterious environmental conditions. In 1992, an El Niño southern oscillation event resulted in complete reproductive failure in a colony of blue-footed boobies,Sula nebouxi,on Isla Isabel in the Pacific Ocean off San Blas, Nayarit, Mexico (21.5°N, 105.5°W). In 1993, the El Niño event had waned and reproductive success was high. The mean sea surface temperature in 1992 was 26.69°, the warmest year for 11 years of data (mean, 25.63°). In 1993, mean sea surface temperature was 25.75°. Plasma levels of testosterone were highest during the egg-laying period in 1993 and declined markedly during incubation. There were no differences between males and females. Comparisons of testosterone levels between 1992 and 1993 (egg-laying time point removed for 1993) showed no significant differences. Thus reproductive failure during an El Niño year was not related to testosterone levels. Baseline plasma levels of corticosterone did not change over the nesting cycle in either sex. There was a trend for plasma levels of corticosterone to be higher in males and females during the earlier stages of breeding in 1992 compared with 1993, and if all levels were combined within years then females showed significantly higher plasma levels of corticosterone in the El Niño year. Plasma levels of corticosterone showed marked increases following capture and handling in both sexes and at every stage of the breeding cycle in each year. There was no variation in the adrenocortical responses to stress with year or stage of nesting in males. However, in females, maximum corticosterone levels were greatest during the parental phase of 1992, the El Niño year, when all nests ultimately failed. Comparisons of the dynamics of corticosterone changes during the capture stress protocol revealed no correlations with body mass in 1992 or 1993. These data suggest that although massive reproductive failure in the El Niño year was not related to testosterone levels, baseline circulating concentrations of corticosterone may have a role in inhibiting onset of breeding. In contrast, after the nesting cycle has been initiated, increased adrenocortical sensitivity to acute stress may be involved in nest abandonment.

Behavioural and hormonal responses of the pied flycatcher to environmental stressors

I investigated the effects of high plasma levels of corticosterone in male pied flycatchers,Ficedula hypoleuca, during the period of territorial establishment and the nestling period. In a second experiment males were exposed to a territorial intruder, a great spotted woodpecker model and a weasel model during the nest-building and nestling periods and their behavioural and hormonal reactions studied. Males were also exposed to handling stress (hormonal study) during these periods. During the period of territorial establishment, corticosterone-treated males, as well as control males, abandoned the territory in which they were captured; however, males in both groups very soon established new territories. During the nestling period, corticosterone-treated males, but not control males, abandoned their nests. During the nest-building period, intact males frequently attacked the territorial intruder but corticosterone-treated males never did; the woodpecker was only rarely attacked by intact males, and the weasel never. During the nestling period, the weasel was not attacked and territorial intruders only rarely; but woodpeckers were frequently attacked. With the progress of the breeding season, male flycatchers significantly reduced their sensitivity, in terms of the adrenocortical response, to all stressors tested. During the nest-building period, corticosterone levels were significantly higher in males exposed to handling, a weasel and a territorial intruder than in unmanipulated males; corticosterone levels in males exposed to a woodpecker did not differ from those in unmanipulated males; and testosterone levels were significantly elevated in males exposed to a woodpecker and to an intruder, but were reduced in males exposed to a weasel. Handling did not affect the testosterone level. During the nestling period, all groups showed low testosterone levels, and only exposure to a weasel and to handling increased corticosterone levels significantly. The results indicate that environmentally induced changes in testosterone and corticosterone secretion can be affected independently from one another, and that there are ecological bases for the differentiated hormonal responses to stress.

Effect of increased maternal corticosterone during lactation on hippocampal corticosteroid receptors, stress response and learning in offspring in the early stages of life

The influence of maternal corticosterone during lactation on the development of the hippocampal corticosteroid receptor system, hypothalamus-pituitary-adrenal axis activity and spatial learning/retention performance was investigated in the rat during postnatal days 11 to 30. We increased the plasma levels of corticosterone by adding the hormone (200 μg/ml) to the drinking water of the dams. When compared to controls corticosterone-nursed offspring displayed: i) higher number of hippocampal type I and type II corticosteroid receptors at 30 days of life, but no changes at 11 and 16 days; ii) higher plasma levels of corticosterone in the basal condition and after 15 min of maternal separation at 11 but not at 16 days; iii) lower adrenal weights at 11 and 16 days, but which were no longer present at the age of 30 days; iv) no difference in performance in the place learning version of the Morris water task and T aquatic maze at 16 days. The present results, together with our previous findings showing that 90-day-old corticosterone-nursed rats have lower basal and restraint stress corticosterone levels and improved learning performance, indicate that the effects of maternal treatment appears only after weaning, thereby suggesting that increased corticosteroid receptors may be responsible, at least partially, for the endocrine and learning modifications induced by pre-weaning corticosterone exposure. The role played by maternal circulating corticosterone during the period of lactation in shaping the characteristics of the hypothalamus-pituitary-adrenal axis and brain of the offspring is outlined.

Modulation of 5HT1A responsiveness in CA1 pyramidal neurons by in vivo activation of corticosteroid receptors.

In this study we describe modulatory effects exerted by in vivo activation of corticosteroid receptors on 5HT responsiveness of rat CA1 pyramidal neurons. In the first series of experiments, adrenalectomized (ADX) rats were injected with corticosterone one hour prior to decapitation (1-1000 micrograms/100 g body weight) after which 5HT1A induced hyperpolarizations were determined in vitro by means of intracellular recordings. It appeared that 5HT responsiveness was dose-dependently affected by corticosterone injections: 5HT responses were relatively large when no corticosteroid receptors were activated (ADX); similar 5HT responses were observed or when both mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) were occupied by injection of high doses of corticosterone (100-1000 micrograms/100 g body weight). However, compared to the latter group, 5HT hyperpolarizations were significantly suppressed in slices from rats that received moderate amounts of corticosterone (10-30 micrograms/100 g). Next, we investigated whether physiological variations of plasma corticosterone levels as occurring in intact rats correlated with the transmitter responsiveness. It was found that high plasma levels of corticosterone due to either stress or exogenous application of high doses of corticosterone correlated with large 5HT-responses in vitro. Interestingly, the large 5HT responses recorded after stress were clearly suppressed by pretreatment with RU38486, a GR antagonist. Altogether, this study presents further evidence that 5HT transmission in hippocampal CA1 area is modulated by differential steroid receptor activation as may occur under physiological circumstances due to different plasma concentrations of corticosterone.

Hormonal correlates of migration and territorial behavior in juvenile willow tits during autumn

This study compared plasma levels of dihydrotestosterone, testosterone, corticosterone, luteinizing hormone, growth hormone, and prolactin in migrating juvenile willow tits with those in territorial juveniles. Both categories of birds were caught in late September. Migrating juveniles had higher plasma levels of corticosterone than territorial juveniles. Only corticosterone secretion was affected by “handling stress” in both migrating and territorial juveniles. However, territorial birds showed a much stronger relationship between these two variables. It is suggested that high corticosterone levels are involved in the emigration of juveniles out of the coniferous forest. Only juveniles were found among the migrating willow tits, and these birds were not well adapted for migration. Migrating juvenile males had less fat stored than did territorial ones. Furthermore, migrating juvenile males had higher liver/somatic index and higher plasma levels of growth hormone than did territorial males. These results indicate that migrating males had been, or were, exposed to food restrictions. The same proportion of migrating and territorial juveniles, males as well as females, had high plasma levels of testosterone. We suggest that these high levels were caused by recent aggressive interactions. To test the hypothesis that high plasma levels of testosterone are important for a juvenile to become a member of a territorial winter group, we performed a field experiment in which juveniles were given testosterone implants (controls were given empty silastic tubes) at the beginning of the territorial establishment period. The same proportion of testosterone-implanted birds and control birds succeeded in becoming members of territorial winter groups. Thus, testosterone does not seem to play an essential role in autumn territoriality, and it does not prevent autumn migration.

Corticosterone-binding proteins and behavioral effects of high plasma levels of corticosterone during the breeding period in the pied flycatcher

In the pied flycatcher there exists an anomaly in the relationship between cortical histology and plasma levels of corticosterone during the breeding period. In an attempt to study this anomaly, binding capacity and binding affinity of plasma corticosterone-binding proteins (CBP) were studied in free-living pied flycatchers during the early and late parts of the breeding period. Binding capacity of CBP showed a significant decrease with the progress of the breeding season in both males and females. During the early parts of the breeding season binding capacity was significantly higher in males than in females. No difference between sexes was observed during the nestling period. In males there also was a seasonal decrease in the binding affinity of CBP. The results show that there is a good relationship between periods with high plasma levels of corticosterone and its binding capacity in the blood. A second study showed that an experimentally increased plasma level of corticosterone during the nestling period drastically reduced reproductive succes. Parents given silastic implants containing corticosterone fed their nestlings less frequently and produced significantly fewer fledglings than did controls. Unlike the control birds, the body weight of the corticosterone-implanted birds did not decrease during the nestling period. Birds given corticosterone implants in which one small hole had been punched, in order to facilitate diffusion of corticosterone, all abandoned their territories and, consequently, these parents produced no fledglings. Thus, the results show that an elevation of plasma levels of corticosterone in adult pied flycatchers during the nestling period affects parental as well as territorial behavior.

Plasma levels of luteinizing hormone and steroid hormones in free-living winter groups of willow tits ( Parus montanus)

Plasma levels of LH, DHT, testosterone, and corticosterone were measured for all members in free-living winter flocks of willow tits, Parus montanus. Hormonal data were related to (1) flock size and (2) age/sex differences. The winter flock defends a large winter territory and shows a well-established social hierarchy in which adults consistently dominate first-year birds. One winter group normally consists of four individuals, two adults and two juveniles. In flocks containing four or five members juvenile willow tits had significantly higher corticosterone values than adults. In small-sized groups, containing three members, all individuals had high plasma levels of corticosterone. No other effects of flock size was found. When data were treated on an age/sex basis, i.e., flock size was not considered, juvenile females were found to have significantly higher plasma levels of testosterone than adult birds, and also significantly higher levels of DHT than juvenile males and adult females. Also, juvenile willow tits had significantly higher plasma levels of corticosterone than adult birds.

Pituitary—adrenal responsiveness of mothers to pups in mice of two inbred strains

Lactating A/J but not C57BL/6J mice had higher plasma levels of corticosterone if their pups were removed, shocked, and then returned in a wire-mesh basket than they did if their pups were removed and an empty basket was returned. The same results were obtained when mothers reared and were tested with pups of the nonmaternal strain. Nulliparous females of both strains showed no greater corticosterone response to shocked pups in a wire basket than they did to the basket alone. Finally, lactating A/J but not C57BL/6J mice had higher plasma levels of corticosterone if they and their litters were undisturbed than if their pups were removed 3 hr 15 min earlier. These results indicate that: (1) stimuli from inaccessible distressed pups can activate the pituitary—adrenal system of lactating mice; (2) interstrain variability observed in this response was due to a difference in maternal genotype; (3) this response does not appear to be common to females of all reproductive states; (4) direct contact with undisturbed pups can also stimulate increased maternal pituitary—adrenal activity in A/J mice.