Elevated Plasma Corticosterone Research Articles

Competition for sucrose pellets in tetrads of male Wistar, Fischer or Sprague–Dawley rats: Is intra-group ranking reflected in the level of anxiety?

Competition for palatable food or fluids within groups of rats has been previously used to mirror intra-group ranking. The paradigm of competition for sucrose pellets in non-food-deprived male Wistar rats was here extended from triads to tetrads aiming at evaluating whether the number of poor-performing rats, those animals being likely to model aspects of human psychopathologies (anxiety/depression/social withdrawal), could be increased. To evaluate potential superiority over the previously used Wistar strain, establishment and stability of the ranking was also assessed in tetrads of male Fischer and Sprague–Dawley rats. Clear and stable rank orders were seen in around 60–70% of both triads and tetrads of Wistar rats: a high-performing, a medium-performing and one (in triads) or two (in tetrads) poor-performing rats were identifiable, indicating that the number of poor-performing rats had increased in tetrads. Comparable rank orders were also seen in tetrads of Fischer and Sprague–Dawley rats. At the end of an extended period of repeated testing, tetrads of these two strains, as well as some selected Wistar tetrads, were tested in the elevated zero-maze and plasma corticosterone levels were determined. The differentiation in competition-performance among cage mates was not paralleled by a difference in performance in the elevated zero-maze or in plasma corticosterone levels in any of the three strains. These data indicate that the level of anxiety in a non-social paradigm, the elevated zero-maze, does not reflect the competition-performance within the home cage and thus, the dominant/subordinate status in this food-competition paradigm may not reflect/being caused by different levels of anxiety.

Dysregulation of the Th1/Th2 cytokine profile is associated with immunosuppression induced by hypothalamic-pituitary-adrenal axis activation in mice

Hypothalamic-pituitary-adrenal (HPA) axis activation-induced immunosuppression is associated with increased concentration of circulating corticosterone and impaired cellular immune responses. The purpose of this study was to investigate the effect of chronic HPA axis activation on the cellular immune response, Th1/Th2 cytokine profile, and concentration of corticosterone. Mice were divided into two groups: a control group comprised of healthy, untreated mice that received no stress, and an HPA axis-activated group that received stress through electric shock (ES). The delayed-type hypersensitivity reaction to dinitrofluorobenzene, splenocyte proliferative response to mitogens Concanavalin A and lipopolysaccharide, Th1 and Th2 profile, and TGF-β1 production were measured in plasma and in culture supernatants. The corticosterone concentration was also measured in plasma. In the ES group, elevated plasma corticosterone concentration was associated with immunosuppression and a significant decrease in plasma concentrations of IL-2, IL-4, and TGF-β1. In vitro IL-2 production in response to Con A was significantly lower in the ES group than in the control group. TGF-β1 production in nonstimulated and stimulated cultures in response to either mitogen was significantly lower in the ES group than in the control group. Plasma concentrations of IFN-γ and IL-10 did not differ significantly between groups. The concentrations of IFN-γ, IL-4, and IL-10 in the supernatants of splenocytes stimulated with either mitogen and IL-4 production by nonstimulated cells were significantly higher in the ES group than in the control group. These results suggest that corticosterone mediates the immunosuppression induced by HPA axis activation, and induces dysregulation of the Th1/Th2 cytokine profile.

Effect of predator-induced maternal stress during gestation on growth in root volesMicrotus oeconomus

We studied the effect of maternal stress evoked by a severe stressor from the cues of predation risk during gestation on the growth of offspring in root volesMicrotus oeconomus Pallas, 1776. Body mass of both male and female offspring was significantly reduced in the period from birth to weaning. Females showed compensatory growth after weaning, whereas males maintained low body mass at weaning into adulthood. Maternal stress led to an elevated plasma corticosterone level in male offspring, but did not affect that of female offspring. Corticosterone levels remained elevated in males from stressed dams into adulthood. Increased levels of plasma corticosterone may have led to the inhibition of pituitary growth hormone and a chronically abnormal energy mobilization, considering the greater energy and metabolic requirements of male offspring, this may account for the sex-specific differences in compensatory growth. We suggest that in the high stress situation, endocrine-based sex-biased effects of maternal stress as a primary factor can lead to long-term physical and ecological consequences for male offspring.

Lithium increases body weight of rats: Relation to thymolysis

Lithium treatment of patients and laboratory animals causes increased body weight. Lithium also elevates the plasma corticosterone levels of rats. Our purpose was to correlate the gain of body weight with the effects of lithium on the thymus gland, the organ most susceptible to stress and to elevated corticosterone levels. Toward this end, it was also necessary to establish a reliable and reproducible model by use of an inbred strain of rats. Female rats of the inbred Lewis strain were injected subcutaneously with lithium chloride or saline for an 18-day period. Necropsies were performed one day after the last treatment or at intervals during the treatment period. Lithium increased body weight gain compared to controls in all the experiments on Lewis rats. Contrary to the body as a whole, lithium caused loss of weight of the thymus gland. The spleen lost less weight than the thymus. Both lithium and nonspecific stress elevate plasma corticosterone and cause thymolysis. Mild nonspecific stress is known to cause increased weight gain in rats as well as in humans. Our data suggest that lithium acts like nonspecific stress to increase weight gain as a consequence of elevated glucocorticoids, manifested in our experiments by thymolysis. This mechanism has not been proposed previously.

Glucocorticoids, 11beta-HSD1 and cognitive function with ageing

Cumulative exposure to high glucocorticoid levels is a major factor advanced to explain individual decline in cognitive function with ageing. Current manipulations to maintain low circulating glucocorticoid levels throughout life (adrenalectomy with low dose corticosterone replacement, neonatal handling), though effective in preventing the emergence of memory deficits with age in rodent models, are however not clinically applicable. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyses the intracellular regeneration of active glucocorticoids from circulating inert 11-keto steroids thus amplifying glucocorticoid levels within specific target cells. In primary hippocampal neurons in vitro, inhibition of 11beta-HSD1 attenuates glucocorticoid-associated neurotoxicity. To determine the importance of 11beta-HSD1 in the ageing brain in vivo, we examined the impact of enzyme loss on hippocampal function using transgenic mice lacking expression of 11beta-HSD1. Wildtype mice develop elevated plasma corticosterone levels with age that correlated with hippocampal specific learning deficits in the watermaze. In contrast, despite similar elevated plasma corticosterone levels, aged 11beta-HSD1 knockout mice show significantly better learning than age-matched wildtype controls; this implicates lower intracellular corticosterone levels through the lack of 11-dehydrocorticosterone re-activation. Consistent with this, aged 11beta-HSD1 knockout mice show lower hippocampal tissue corticosterone levels than in wildtype controls. At the cellular level, enhanced hippocampal long-term potentiation in the CA1 region of aged 11beta-HSD1 knockout mice may, in part, underlie the improved cognitive function.

Stress Hormones: A Link between Maternal Condition and Sex‐Biased Reproductive Investment

In species where offspring fitness is sex-specifically influenced by maternal reproductive condition, sex allocation theory predicts that poor-quality mothers should invest in the evolutionarily less expensive sex. Despite an accumulation of evidence that mothers can sex-specifically modulate investment in offspring in relation to maternal quality, few mechanisms have been proposed as to how this is achieved. We explored a hormonal mechanism for sex-biased maternal investment by measuring and experimentally manipulating baseline levels of the stress hormone corticosterone in laying wild female European starlings (Sturnus vulgaris) and examining effects on sex ratio and sex-specific offspring phenotype adjustment. Here we show that baseline plasma corticosterone is negatively correlated with energetic body condition in laying starlings, and subsequent experimental elevation of maternal baseline plasma corticosterone increased yolk corticosterone without altering maternal condition or egg quality per se. Hormonal elevation resulted in the following: female-biased hatching sex ratios (caused by elevated male embryonic mortality), lighter male offspring at hatching (which subsequently grew more slowly during postnatal development), and lower cell-mediated immune (phytohemagglutinin) responses in males compared with control-born males; female offspring were unaffected by the manipulation in both years of the study. Elevated maternal corticosterone therefore resulted in a sex-biased adjustment of offspring quality favorable to female offspring via both a sex ratio bias and a modulation of male phenotype at hatching. In birds, deposition of yolk corticosterone may benefit mothers by acting as a bet-hedging strategy in stochastic environments where the correlation between environmental cues at laying (and therefore potentially maternal condition) and conditions during chick-rearing might be low and unpredictable. Together with recent studies in other vertebrate taxa, these results suggest that maternal stress hormones provide a mechanistic link between maternal quality and sex-biased maternal investment in offspring.

Behaviour of food restricted broilers during rearing and lay—effects of an alternative feeding method

Broiler breeders are subjected to quantitative food restriction in order to control their growth, and this restriction is particularly severe during rearing. While such restriction improves some welfare problems associated with ad libitum feeding, it causes others: birds routinely show abnormal oral behaviours and have elevated plasma corticosterone concentration (PCC) and changes in white blood cell counts (WBCs). The aim of this study was to examine if feeding birds qualitatively restricted diets ad libitum during rearing could reduce signs of impaired welfare, as judged by behaviour and blood indices of stress, while also meeting commercially desired growth rates and uniformity. Furthermore, we examined what carry-over effects such a feeding method had on birds in the laying phase when all birds were fed on a conventional quantitative restriction regime. During rearing (1–20 weeks of age), pens of birds were either fed limited amounts of standard basal diets (Control, i.e. quantitative restriction), or ad libitum diets consisting of standard basal diets with gradually increasing levels of calcium propionate (CaP) and a constant level of oat hulls (OH), designated CaP + OH (i.e. qualitative restriction). Results showed that, during rearing, weights and weight uniformity were similar for the two groups. During feeding motivation tests, Control birds always consumed more food than CaP + OH birds. This suggests that Control birds were more highly motivated to feed than CaP + OH birds, although care has to be taken in interpreting these results. Treatment did not affect PCCs or WBCs, but there was a general decline in PCCs with bird age. All reported behaviours differed significantly between treatment groups during rearing, but disappeared during lay when all birds were fed a similar amount of food. Control birds spent up to 50% of time in object pecking during rearing periods, but this behaviour was virtually non-existent in birds in the qualitative feeding regime. Overall, the results indicate that broiler breeders can be successfully limited in growth rates by qualitative food restriction and this results in significant changes of behaviour that suggest improvements to bird welfare.

Antipyretic effect of oral sodium salicylate after an intravenous E. coli LPS injection in broiler chickens

1. A study was set up to investigate the influence of sodium salicylate on fever and acute phase reaction after lipopolysaccharide (LPS) injection in broiler chickens. 2. An acute phase reaction was provoked through the intravenous injection of Escherichia coli LPS. Four oral doses of sodium salicylate were tested. Apart from body temperature, other inflammation indices, such as plasma corticosterone and ceruloplasmin, serum thromboxane B2 and zinc concentrations were monitored. 3. Intravenous LPS induced a fever of about 1°C. A dose-dependent attenuation of the fever response of the chickens in the salicylate treated groups was observed. LPS-injected chickens also showed elevated plasma corticosterone and ceruloplasmin, while serum thromboxane and zinc concentrations decreased. Except for thromboxane B2, no linear relationship with increasing salicylate dose could be shown for the other blood variables. 4. These data confirm that sodium salicylate is an effective antipyretic agent after injection of LPS in chickens, if used at an appropriate dosage. No dose-related change could be found for the other inflammation indices.

A stress-induced anxious state in male rats: Corticotropin-releasing hormone induces persistent changes in associative learning and startle reactivity

Exposure to intense inescapable stressors induces a persistent anxious state in rats. The anxious state is evident as increased sensory reactivity and enhanced associative learning. We examine whether similar neurobehavioral changes are observed after intracerebroventricular (ICV) administration of corticotropin releasing hormone (CRH). Two behaviors were observed: acoustic startle responses (ASRs) and acquisition of the classically conditioned eyeblink response. Male Sprague-Dawley rats were administered ICV CRH either in a single dose (1.0 microg/rat) or in three doses each separated by 30 min. Exaggerated ASRs were evident 2 hours after either CRH treatment; however, only the rats given three injections exhibited a persistently exaggerated ASR apparent 24 hours after CRH treatment. Rats administered three injections of CRH also exhibited faster acquisition of the eyeblink conditioned response beginning 24 hours after treatment. Yet, we did not find evidence for a persistent activation of the HPA-axis response; three CRH injections did not lead to elevated basal plasma corticosterone levels the following morning. Repeated treatment with CRH over a 1.5-hour period models some of the behavioral changes observed after exposure to intense inescapable stressors.

Effects of Chronic Social Stress on Neuroendocrine Responsiveness to Challenge with Ethanol, Dexamethasone and Corticotropin-Releasing Hormone

Neuroendocrine and behavioral profiles of group-housed rodents differ from those of singly-housed ones. Subordinate rats have elevated plasma corticosterone (CORT) concentration and impaired activity of the hypothalamic-pituitary-adrenal (HPA) axis compared to dominant cagemates. However, little is known about the effects of social hierarchy on other stress-related hormones. We examined plasma prolactin (PRL) and CORT responses to saline and ethanol (EtOH) injections, and 1 month later to dexamethasone (DEX) and corticotropin-releasing hormone (CRH) challenges of group- (triad) and single-housed male rats over a period of 225 days. Social status was determined from behaviors displayed upon initial triad housing. Subordinate rats had lower basal PRL and higher CORT compared to dominant rats. The injection of EtOH (1.25 g/kg) depressed PRL and elevated CORT levels significantly more than the saline injection only in dominant and singly-housed rats. DEX increased PRL levels, most strikingly in dominant rats, and suppressed CORT only in dominant rats. After CRH challenge, plasma CORT increased in all groups, subdominant and subordinate rats displaying blunted responses. Our data demonstrate that social rank and housing conditions affect plasma PRL and CORT concentrations, and modify responses to EtOH, possibly reflecting impairments of HPA axis regulation in socially-housed rats.

Stress Hormones: A Link between Maternal Condition and Sex-Biased Reproductive Investment

In species where offspring fitness is sex‐specifically influenced by maternal reproductive condition, sex allocation theory predicts that poor‐quality mothers should invest in the evolutionarily less expensive sex. Despite an accumulation of evidence that mothers can sex‐specifically modulate investment in offspring in relation to maternal quality, few mechanisms have been proposed as to how this is achieved. We explored a hormonal mechanism for sex‐biased maternal investment by measuring and experimentally manipulating baseline levels of the stress hormone corticosterone in laying wild female European starlings (Sturnus vulgaris) and examining effects on sex ratio and sex‐specific offspring phenotype adjustment. Here we show that baseline plasma corticosterone is negatively correlated with energetic body condition in laying starlings, and subsequent experimental elevation of maternal baseline plasma corticosterone increased yolk corticosterone without altering maternal condition or egg quality per se. Hormonal elevation resulted in the following: female‐biased hatching sex ratios (caused by elevated male embryonic mortality), lighter male offspring at hatching (which subsequently grew more slowly during postnatal development), and lower cell‐mediated immune (phytohemagglutinin) responses in males compared with control‐born males; female offspring were unaffected by the manipulation in both years of the study. Elevated maternal corticosterone therefore resulted in a sex‐biased adjustment of offspring quality favorable to female offspring via both a sex ratio bias and a modulation of male phenotype at hatching. In birds, deposition of yolk corticosterone may benefit mothers by acting as a bet‐hedging strategy in stochastic environments where the correlation between environmental cues at laying (and therefore potentially maternal condition) and conditions during chick‐rearing might be low and unpredictable. Together with recent studies in other vertebrate taxa, these results suggest that maternal stress hormones provide a mechanistic link between maternal quality and sex‐biased maternal investment in offspring.

Blockage of glucocorticoid, but not mineralocorticoid receptors prevents the persistent increase in circulating basal corticosterone concentrations following stress in the rat

Exposure to a single session of intense inescapable stressors results in elevations of plasma corticosterone levels selective to the trough of the circadian rhythm that last for several days after stressor cessation. In the present study, we examined whether this stress-induced alteration in the regulation of the circadian trough is dependent upon glucocorticoid and/or mineralocorticoid receptor activation during stress. Pre-treatment with the mineralocorticoid receptor (MR) antagonist, spironolactone (RU-28318; 50 mg/kg, s.c.), and/or the glucocorticoid receptor (GR) antagonist, mifepristone (RU-38486; 50 mg/kg, s.c.) 1 h before inescapable stress (40, 2.0-mA tail-shocks delivered over a 1 h period) had no effect on the acute plasma corticosterone response to inescapable stress. Treatment with the MR antagonist alone did not affect the appearance of basal corticosterone elevations in stressed rats. However, the elevated trough plasma corticosterone levels were no longer evident in rats treated previously with the GR antagonist either alone or in combination with the MR antagonist. GR activation during stressor exposure appears to be necessary for the development of subsequent basal corticosterone elevations.

BDNF protects against stress-induced impairments in spatial learning and memory and LTP.

The present study investigated whether infusion of brain-derived neurotrophic factor (BDNF) could ameliorate stress-induced impairments in spatial learning and memory as well as hippocampal long-term potentiation (LTP) of rats. Chronic immobilization stress (2 h/day x 7 days) significantly impaired spatial performance in the Morris water maze, elevated plasma corticosterone, and attenuated LTP in hippocampal slices from these animals as compared with normal control subjects. BDNF was infused into the left hippocampus (0.5 mul/h) for 14 days, beginning 7 days before the stress exposure. The BDNF group was protected from the deleterious effects of stress and performed at a level indistinguishable from normal control animals despite the presence of elevated corticosterone. BDNF alone and sham infusions had no effect on performance or LTP. These results demonstrate that spatial learning and memory, and LTP, a candidate neural substrate of learning and memory, are compromised during chronic stress, and may be protected by BDNF administration.

The role of central corticotropin-releasing hormone in the anorexic and endocrine effects of the bacterial T cell superantigen, Staphylococcal enterotoxin A

Bacterial superantigens, such as the staphylococcal enterotoxins, exert a strong capacity for in vivo stimulation of T cell proliferation and cytokine production. Previously, staphylococcal enterotoxin A (SEA) was shown to induce an anorexic effect under novel contextual conditions of testing, and produced an increase in plasma ACTH and corticosterone levels in C57BL/6J mice. In the present study, the role of corticotropin releasing hormone (CRH) in promoting these effects of SEA was addressed via intracerebroventricular (icv) administration of α-helical CRH 9–41 (αhCRH), a non-selective CRH receptor antagonist, and astressin-2B, a selective CRH receptor 2 antagonist. The efficacy of αhCRH and astressin-2B in blocking anorexic responses to CRH and urocortin under the current conditions of testing was first confirmed. Subsequently, it was found that αhCRH (20 μg icv), but not astressin-2B (10 and 25 μg icv), significantly attenuated the anorexia induced by SEA. This suggested that central CRH is involved in mediating the anorexia induced by SEA, but potentially through CRH receptor 1. Additional results revealed that plasma ACTH stimulation in response to SEA was not significantly attenuated by either antagonist administered icv. However, the plasma corticosterone elevation showed a modest, but significant, attenuation in SEA challenged mice given αhCRH. These data suggest a possible influence of central CRH on adrenocorticoid activity subsequent to SEA challenge. More importantly, it appears that central activation of CRH receptors is a consequence of SEA challenge, and this likely contributes to its anorexic effects.

Effects of active shock avoidance learning on hippocampal neurogenesis and plasma levels of corticosterone

Hippocampal granule neurons that are newly formed during adulthood might be involved in learning and memory processes. Experimental data suggest that only hippocampus-dependent learning tasks stimulate neurogenesis. To further address this issue, the effects of active shock avoidance (ASA) learning on hippocampal progenitor proliferation and survival of newly formed cells were investigated. ASA training, although considered as hippocampus-independent, is known to induce several neurobiological alterations in the hippocampus. Adult Wistar rats were trained in a shuttle box using a 1-day or 4-day paradigm and brains were analyzed for the mitotic marker Ki-67. Effects on survival of newly generated cells were examined by immunocytochemistry for 5-bromo-2-deoxyuridine (BrdU), which was injected 1 week before the training. Neither proliferation nor survival was affected by the ASA learning task. Because elevated glucocorticoid levels have a negative impact on hippocampal neurogenesis, blood samples were taken throughout the 4-day training paradigm. Both trained animals and control rats that were only placed in the shuttle box without receiving foot shocks showed a similar rise in corticosterone, enabling us to exclusively investigate the effects of ASA learning on neurogenesis without differential interference of stress between groups. On the other hand, the finding that ASA induced elevations in plasma corticosterone, but did not influence proliferation or survival of newly formed cells, indicates that this type of stress does not affect neurogenesis. The present study shows that, in line with the existing data on other hippocampus-independent learning tasks, ASA training has no effect on hippocampal neurogenesis.

A possible mechanism for the action of adrenomedullin in brain to stimulate stress hormone secretion.

Adrenomedullin (AM) has been reported to have actions at each level of the hypothalamo-pituitary-adrenal (HPA) axis, suggesting that the peptide plays a role in the organization of the neuroendocrine responses to stress. We examined the mechanism by which AM regulates the central nervous system branch of the HPA axis as well as the possible role of AM in the modulation of the releases of two other hormones, prolactin and GH, whose secretions also are altered by stress. Intracerebroventricular administration of AM led to elevated plasma corticosterone levels in unrestrained, conscious male rats. This effect was abrogated by pretreatment with a CRH antagonist, suggesting that AM activates the HPA axis by causing the release of CRH into hypophyseal portal vessels. In addition, AM given intracerebroventricularly stimulated the release of prolactin but did not alter the secretion of GH. We propose that AM produced in the brain may be an important neuromodulator of the hormonal stress response.

Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice

Indigenous microbiota have several beneficial effects on host physiological functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. To test the idea that such microbes may affect the development of neural systems that govern the endocrine response to stress, we investigated hypothalamic-pituitary-adrenal (HPA) reaction to stress by comparing germfree (GF), specific pathogen free (SPF) and gnotobiotic mice. Plasma ACTH and corticosterone elevation in response to restraint stress was substantially higher in GF mice than in SPF mice, but not in response to stimulation with ether. Moreover, GF mice also exhibited reduced brain-derived neurotrophic factor expression levels in the cortex and hippocampus relative to SPF mice. The exaggerated HPA stress response by GF mice was reversed by reconstitution with Bifidobacterium infantis. In contrast, monoassociation with enteropathogenic Escherichia coli, but not with its mutant strain devoid of the translocated intimin receptor gene, enhanced the response to stress. Importantly, the enhanced HPA response of GF mice was partly corrected by reconstitution with SPF faeces at an early stage, but not by any reconstitution exerted at a later stage, which therefore indicates that exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation. These results suggest that commensal microbiota can affect the postnatal development of the HPA stress response in mice.

Losartan may prevent the elevation of plasma glucose, corticosterone and catecholamine levels induced by chronic stress

Stress is a stimulus that activates the hypothalamic pituitary adrenal (HPA) axis and sympathetic nervous system (SNS). Increased activity of the SNS causes to increment or impairment in blood pressure, heart rate, body temperature and plasma glucose and adreno- corticotrophic hormone (ACTH) levels. Angiotensin II (Ang II), which is a product of the renin-angiotensin system (RAS), is an important factor affecting the activity of the SNS and responses to stress. We suggest that the blockade of Ang II may be worthwhile in the prevention and treatment of diabetes mellitus and cardiovascular diseases affected by stress. Therefore, we investigated the effects of immobilisation stress on blood glucose, norepinephrine (NE), epinephrine (E) and corticosterone levels and the effects of an Ang II receptor antagonist, losartan, on these parameters. The rats were kept in small cylindrical cages for 60 min/day for 10 consecutive days to perform chronic immobilisation stress. Losartan (10 mg/kg) was given daily by gavage to Losartan (L) and Losartan + Chronic Stress (L+CS) groups. Control (C) and Chronic Stress (CS) groups received an equal volume of saline daily by gavage for 10 days. After the last stress regimen, blood samples were collected for plasma glucose, NE, E and corticosteroid measurements. Plasma glucose, NE, E and corticosterone levels in the CS Group increased significantly compared with the C group. In Group L+CS, the plasma glucose, NE, E and corticosterone levels decreased significantly vs. Group CS. In Group L there was no significant difference vs. Group C. It can be speculated that chronic blockade of RAS may decrease the excess sympathetic responses to stress in cardiovascular diseases and prevent the likely development of Type II diabetes mellitus.

Behavioral sensitivity to corticosterone in juveniles of the wall lizard, Podarcis muralis

Reptiles exposed to stressful conditions respond with increases in plasma levels of corticosterone (CORT). The outcome of such hormonal fluctuations can affect the organism's physiology and behavior; however, relatively few studies in reptiles have progressed past the effects of stress on the plasma levels of CORT. The purpose of this study was to investigate the effects of CORT on lizard behavior. We focused on activity and thermoregulation of juveniles of the wall lizard, Podarcis muralis. Juveniles with experimentally elevated plasma CORT concentrations showed a higher moving rate and spent a greater amount of time moving. They also spent more time being involved in attempts to escape from a terrarium. This enhanced locomotor activity was associated with significant changes in thermoregulatory behavior, as CORT-increased individuals had reduced thermoregulatory activity than the controls. The same pattern of results was obtained in nature and under laboratory conditions. Thus, CORT levels appear to mediate an important trade-off between locomotor activity and thermoregulation. To our knowledge, this is the first time that the effect of CORT on lizard thermoregulation has been examined.

The role of IL-1β in stress-induced sensitization of proinflammatory cytokine and corticosterone responses

Proinflammatory cytokines often sensitize neuronal, hormonal, and behavioral responses to subsequent challenge. Recently, it was observed that exposure to inescapable tailshock enhances peripheral and central proinflammatory cytokine and corticosterone (CORT) responses to subsequent immune challenge up to 4 days later. Thus, we examined the role of central interleukin-1β (IL-1β) in stress-induced sensitization of proinflammatory cytokine and CORT responses to a subsequent immune challenge. Rats were administered IL-1 receptor antagonist (IL-1ra) or vehicle into the intra-cisterna magna 1 h prior to tailshock (100, 1.6 mA 5 s shocks) exposure. Twenty-four hours later, rats were challenged i.p. with 10 μg/kg lipopolysaccharide (LPS) and killed 1 h later. IL-1ra had no effect on basal proinflammatory cytokines, but completely blocked the stress-induced enhancement in central and pituitary IL-1β and plasma IL-6 release following LPS challenge. IL-1ra had no effect on stress-induced enhancement in CORT responses following LPS challenge. Additional rats were administered i.c.v. hrIL-1β or vehicle and returned to their home cage. Twenty-four hours later, rats were challenged i.p. with either saline or 10 μg/kg LPS and killed 1 h later. Central hrIL-1β administration significantly elevated central IL-1β levels and plasma CORT following LPS challenge compared with vehicle-injected controls. These data demonstrate that elevations in central IL-1β, whether stress-induced or exogenously administered, are sufficient for sensitizing central IL-1β and CORT responses to subsequent immune challenge. However, during times of stress, exogenous central IL-1ra administration only blocked sensitization of subsequent central IL-1β responses, not CORT responses, suggesting other factors during the stress response can sensitize CORT responses.