Stress-induced Corticosterone Research Articles

Androgen and glucocorticoid profiles throughout extended uniparental paternal care in the eastern hellbender salamander (Cryptobranchus a. alleganiensis)

The behavioral endocrinology associated with reproduction and uniparental male care has been studied in teleosts, but little is known about hormonal correlates of uniparental male care in other ectotherms. To address this gap, we are the first to document the seasonal steroid endocrinology of uniparental male hellbender salamanders during the transition from pre-breeding to nest initiation, and through the subsequent eight months of paternal care. In doing so, we investigated the correlates of nest fate and clutch size, exploring hellbenders’ alignment with several endocrinological patterns observed in uniparental male fish. Understanding the endocrinology of hellbender paternal care is also vital from a conservation perspective because high rates of nest failure were recently identified as a factor causing population declines in this imperiled species. We corroborated previous findings demonstrating testosterone and dihydrotestosterone (DHT) to be the primary androgens in hellbender reproduction, and that cortisol circulates as the most abundant glucocorticoid. However, we were unable to identify a prolactin or a “prolactin-like” peptide in circulation prior to or during parental care. We observed ∼ 80 % declines in both primary androgens during the transition from pre-breeding to nest initiation, and again as paternal care progressed past its first month. In the days immediately following nest initiation, testosterone and DHT trended higher in successful individuals, but did not differ with males’ clutch size. We did not observe meaningful seasonality in baseline glucocorticoids associated with breeding or nesting. In contrast, stress-induced glucocorticoids were highest at pre-breeding and through the first two months of care, before declining during the latter-most periods of care as larvae approach emergence from the nest. Neither baseline nor stress-induced glucocorticoids varied significantly with either nest fate or clutch size. Both stress-induced cortisol and corticosterone were positively correlated with total length, a proxy for age in adult hellbenders. This is consistent with age-related patterns in some vertebrates, but the first such pattern observed in a wild amphibian population. Generally, we found that nesting hellbenders adhere to some but not all of the endocrinological patterns observed in uniparental male teleosts prior to and during parental care.

Stress response of fire salamander larvae differs between habitat types.

The larvae of the European fire salamander (Salamandra salamandra) can inhabit two different habitats: streams and ponds. Streams are characterized by lower predation risks and higher food availability. Thus, ponds are considered a less suitable habitat. To investigate the differential impacts of these two habitats on larval physiology, we measured the stress response of larvae. After successfully validating the measure of water-borne corticosterone release rates in fire salamander larvae, we measured the baseline and stress-induced corticosterone of 64 larvae from ponds and streams in the field. We found that larvae in ponds have a higher baseline and stress-induced corticosterone levels. Additionally, we performed a reciprocal transplant experiment (RTE) and tested whether larvae can adapt their stress responses to changing habitats. After two weeks, we did not find an increase in corticosterone levels when comparing stress-induced corticosterone values with baseline corticosterone values in larvae transferred into ponds, irrespective of their habitat of origin. However, larvae transferred into streams still exhibited an increase in the stress-induced corticosterone response in comparison with the baseline values. These results show that non-invasive hormone measurements can provide information on the habitat quality and potential adaptation and thus emphasize the potential for its use in conservation efforts.

Unpredictable Mixed-Valence Outcomes Induce a Chronic and Reversible Generalized Anxiety-like Phenotype in Male Mice

BackgroundClinical anxiety is a generalized state characterized by feelings of apprehensive expectation and is distinct from momentary responses such as fear or stress. In contrast, most laboratory tests of anxiety focus on acute responses to momentary stressors. MethodsApprehensive expectation was induced by subjecting mice (for 18 days) to manipulations in which a running response (experiment 1) or a conditioned stimulus (experiment 2) were unpredictably paired with reward (food) or punishment (footshock). Before this treatment, the mice were tested in an open field and light/dark box to assess momentary responses that are asserted to reflect state anxiety. After treatment, the mice were assessed for state anxiety in an elevated plus maze, social interaction test, startle response test, intrusive object burying test, and stress-induced corticosterone elevations. In experiment 3, we treated mice similarly to experiment 1, but after mixed-valence training, some mice received either no additional training, additional mixed-valence training, or were shifted to consistent (predictable) reinforcement with food.Results: We consistently observed an increase in anxiety-like behaviors after the experience with mixed-valence unpredictable reinforcement. This generalized anxiety persisted for at least 4 weeks after the mixed-valence training and could be reversed if the mixed-valence training was followed by predictable reinforcement with food. ConclusionsResults indicate that experience with unpredictable reward/punishment can induce a chronic state analogous to generalized anxiety that can be mitigated by exposure to stable, predictable conditions. This learned apprehension protocol provides a conceptually valid model for the study of the etiology and treatment of anxiety in laboratory animals.

Repetitive neonatal procedural pain affects stress-induced plasma corticosterone increase in young adult females but not in male rats.

Exposure to repetitive painful procedures in the neonatal intensive care unit results in long-lasting effects, especially visible after a "second hit" in adulthood. As the nociceptive system and the hypothalamic-pituitary-adrenal (HPA) axis interact and are vulnerable in early life, repetitive painful procedures in neonates may affect later-life HPA axis reactivity. The first aim of the present study was to investigate the effects of repetitive neonatal procedural pain on plasma corticosterone levels after mild acute stress (MAS) in young adult rats. Second, the study examined if MAS acts as a "second hit" and affects mechanical sensitivity. Fifty-two rats were either needle pricked four times a day, disturbed, or left undisturbed during the first neonatal week. At 8weeks, the animals were subjected to MAS, and plasma was collected before (t0), after MAS (t20), and at recovery (t60). Corticosterone levels were analyzed using an enzyme-linked immunosorbent assay, and mechanical sensitivity was assessed with von Frey filaments. Results demonstrate that repetitive neonatal procedural pain reduces stress-induced plasma corticosterone increase after MAS only in young adult females and not in males. Furthermore, MAS does not affect mechanical sensitivity in young adult rats. Altogether, the results suggest an age- and sex-dependent effect of repetitive neonatal procedural pain on HPA axis reprogramming.

Comparing fear responses of two lizard species across habitats varying in human impact

Abstract Animals that are successful in urban habitats often have reduced antipredator responses toward people (sometimes called “fear” responses). However, few studies test whether sympatric species differ in their responses to humans, which may explain differing sensitivities to urbanization. Here, we quantified the behavioral and physiological responses to humans in two lizard species, side-blotched lizards (Uta stansburiana) and western fence lizards (Sceloporus occidentalis), across three different habitat types that vary in human impact: natural habitats with low levels of human activity, natural habitats with high levels of human activity, and urban habitats. We found that side-blotched lizards had longer flight initiation distances, were found closer to a refuge, and were more likely to hide than fence lizards, behaviors that could indicate greater fearfulness. Both lizard species were found closer to a refuge and were also more likely to hide in the urban habitat than in the natural habitat with low human impact, which could represent adaptive behaviors for increased risks in urban areas (e.g. cats). Western fence lizards exhibited lower body sizes and conditions in the habitats with moderate and high levels of human activity, whereas these traits did not differ among habitats in side-blotched lizards. Baseline and stress-induced corticosterone concentrations did not differ across habitats for both species, suggesting that human-impacted habitats were not stressful or that lizards had undergone habituation-like processes in these habitats. Taken together, our results highlight the importance of standardized measurements across multiple species in the same habitats to understand differential responses to human-induced environmental change.

Glucocorticoids and land cover: a largescale comparative approach to assess a physiological biomarker for avian conservation.

As humans alter landscapes worldwide, land and wildlife managers need reliable tools to assess and monitor responses of wildlife populations. Glucocorticoid (GC) hormone levels are one common physiological metric used to quantify how populations are coping in the context of their environments. Understanding whether GC levels can reflect broad landscape characteristics, using data that are free and commonplace to diverse stakeholders, is an important step towards physiological biomarkers having practical application in management and conservation. We conducted a phylogenetic comparative analysis using publicly available datasets to test the efficacy of GCs as a biomarker for large spatial-scale avian population monitoring. We used hormone data from HormoneBase (51 species), natural history information and US national land cover data to determine if baseline or stress-induced corticosterone varies with the amount of usable land cover types within each species' home range. We found that stress-induced levels, but not baseline, positively correlated with per cent usable land cover both within and across species. Our results indicate that GC concentrations may be a useful biomarker for characterizing populations across a range of habitat availability, and we advocate for more physiological studies on non-traditional species in less studied populations to build on this framework. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

How does maternal age influence reproductive performance and offspring phenotype in the snow petrel (Pagodroma nivea)?

In wild vertebrates, the increase of breeding success with advancing age has been extensively studied through laying date, clutch size, hatching success, and fledging success. However, to better evaluate the influence of age on reproductive performance in species with high reproductive success, assessing not only reproductive success but also other proxies of reproductive performance appear crucial. For example, the quality of developmental conditions and offspring phenotype can provide robust and complementary information on reproductive performance. In long-lived vertebrate species, several proxies of developmental conditions can be used to estimate the quality of the produced offspring (i.e., body size, body condition, corticosterone levels, and telomere length), and therefore, their probability to survive. By sampling chicks reared by known-aged mothers, we investigated the influence of maternal age on reproductive performance and offspring quality in a long-lived bird species, the snow petrel (Pagodroma nivea). Older females bred and left their chick alone earlier. Moreover, older females had larger chicks that grew faster, and ultimately, those chicks had a higher survival probability at the nest. In addition, older mothers produced chicks with a higher sensitivity to stress, as shown by moderately higher stress-induced corticosterone levels. Overall, our study demonstrated that maternal age is correlated to reproductive performance (hatching date, duration of the guarding period and survival) and offspring quality (body size, growth rate and sensitivity to stress), suggesting that older individuals provide better parental cares to their offspring. These results also demonstrate that maternal age can affect the offspring phenotype with potential long-term consequences.

Body condition and corticosterone stress response, as markers to investigate effects of human activities on Adélie penguins (Pygoscelis adeliae)

IntroductionIn Antarctica, there is growing concern about the potential effect of anthropogenic activities (i.e., tourism, research) on wildlife, especially since human activities are developing at an unprecedented rate. Although guidelines exist to mitigate negative impacts, fundamental data are currently lacking to reliably assess impacts. Physiological tools, such as circulating corticosterone levels, appear promising to assess the potential impact of human disturbance on Antarctic vertebrates.MethodsIn this study, we compared the body condition, and the physiological sensitivity to stress (i.e., basal and stress-induced corticosterone level) of adult and chick Adélie penguins between a disturbed and an undisturbed area (i.e., 2 colonies located in the middle of a research station exposed to intense human activities and 2 colonies located on protected islands with minimal human disturbance).ResultsWe did not find any significant impact of human activities on body condition and corticosterone levels in adults (incubating adults, brooding adults). In chicks, there were significant inter-colony variations in stress-induced corticosterone levels. Specifically, the chicks from the disturbed colonies tended to have higher stress-induced corticosterone levels than the chicks from the protected areas although this difference between areas was not significant. In addition, and independently of human disturbance we also found significant differences in adult body condition, and chick corticosterone level between colonies.DiscussionOverall, our study suggests that this species is not dramatically impacted by human activities, at least when humans and penguins have cohabited for several decades. Our results support therefore the idea that this species is likely to be tolerant to human disturbance and this corroborates with the persistence of Adélie penguin colonies in the middle of the research station. However, our results also suggest that chicks might be more sensitive to human disturbance than adults and might therefore potentially suffer from human disturbance. Our study also suggests that specific individual and environmental variables outweigh the potential minor impact of human disturbance on these variables. Combining corticosterone with complementary stress-related physiological markers, such as heart rate, may strengthen further studies examining whether human disturbance may have subtle detrimental impacts on individuals.

Molecular changes in hippocampal energy metabolism in mice selectively bred for extremes in stress reactivity: relevance of mitochondrial dysfunction for affective disorders.

Affective disorders, such as major depression, are frequently associated with metabolic disturbances involving mitochondria. Although dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is known to alter energy metabolism, the precise mechanisms linking stress and metabolic disturbances are not sufficiently understood. We used a mouse model of affective disorders to investigate the impact of a genetic predisposition for extremes in stress reactivity on behavioural and metabolic phenotypes as well as energy metabolism. Adult males of three independent mouse lines selectively bred for high, intermediate or low HPA axis reactivity were tested for exploratory and locomotor activity as well as stress-coping behaviour. Additionally, basal and stress-induced plasma corticosterone levels, body weight, food intake and body composition were measured. At the molecular level, the hippocampal transcriptome was analysed using microarray, serial analysis of gene expression and qRT-PCR. Finally, mitochondrial DNA copy number, damages and mitochondrial respiration were assessed. We found clear effects of the differential stress reactivity on the behavioural, morphometric and metabolic measures. Remarkably, the hyperactive behavioural and neuroendocrine stress-coping style of High Reactivity mice was associated with significant changes in the expression of an extended list of genes involved in energy metabolism and several mitochondrial functions. Yet, only minor changes were found in mitochondrial DNA copy number, damages and respiration. Thus, our findings support a prominent role of glucocorticoids in shaping the major endophenotypes of the stress reactivity mouse model and contribute towards understanding the important role of HPA axis dysregulation and changes in energy metabolism in the pathophysiology of affective disorders.

Combined Supplementation of Clostridium butyricum and Bifidobacterium infantis Diminishes Chronic Unpredictable Mild Stress-Induced Intestinal Alterations via Activation of Nrf-2 Signaling Pathway in Rats.

Exposure to long-term chronic unpredictable mild stress (CUMS) can cause redox imbalance and inflammation, which may affect the integrity of the gut barrier. The present study was conducted to investigate the effects of a probiotics bacterium mixture, including Clostridium butyricum (C. butyricum) and Bifidobacterium infantis (B. infantis), on the intestinal homeostasis in rats exposed to multiple low-intensity stressors for 28 days. The mechanism of CUMS-induced altered intestinal homeostasis was evaluated by focusing on the nuclear factor-E2-related factor-2 (Nrf-2) pathway. In contrast to the CUMS group, probiotic mixture supplementation significantly (p < 0.01) reversed the stress-induced elevated corticosterone level, protein and lipid oxidation, and increased enzymatic and non-enzymatic antioxidant levels, as well as upregulated Nrf-2/HO-1 pathway. Probiotics supplementation further significantly (p < 0.01) decreased the CUMS-induced inflammation, altered T-lymphocyte levels, and suppressed the protein expression of nuclear factor kappa B (NF-κB) in rat intestines. Improvement in histological changes and intestinal barrier integrity further validate the beneficial effects of probiotic mixtures on CUMS-induced altered intestinal morphology. In conclusion, our results suggest that the combination of C. butyricum and B. infantis significantly attenuated CUMS-induced oxidative stress, inflammation, and T-lymphocyte modulation by upregulating Nrf-2/HO-1 signaling and inhibiting NF-κB expression in rat intestine.

Ophidiomycosis is associated with alterations in the acute glycemic and glucocorticoid stress response in a free-living snake species

Emerging fungal pathogens are a direct threat to vertebrate biodiversity. Elucidating the mechanisms by which mycoses impact host fitness is an important step towards effective prediction and management of disease outcomes in populations. The vertebrate acute stress response is an adaptive mechanism that allows individuals to meet challenges to homeostasis and survival in dynamic environments. Disease may cause stress, and coping with fungal infections may require shifts in resource allocation that alter the ability of hosts to mount an acute response to other external stressors. We examined the glucocorticoid and glycemic response to acute capture stress in a population of free-living pygmy rattlesnakes, Sistrurus miliarius, afflicted with an emerging mycosis (ophidiomycosis) across seasons. In all combinations of disease status and season, acute capture stress resulted in a significant glucocorticoid and glycemic response. While disease was not associated with elevated baseline or stress-induced corticosterone (CORT), disease was associated with an increased glucocorticoid stress response (post-stress minus baseline) across seasons. Both baseline and stress-induced glucose were lower in snakes with ophidiomycosis compared to uninfected snakes. The relationship between glucose and pre- and post-stress CORT depended on infection status, and positive correlations were only observed in uninfected snakes. The variables which explained CORT and glucose levels were different. The pattern of CORT was highly seasonal (winter high – summer low) and negatively related to body condition. Glucose, on the other hand, did not vary seasonally or with body condition and was strongly related to sex (male high – female low). Our results highlight the fact that circulating CORT and glucose are sensitive to different intrinsic and extrinsic predictor variables and support the hypothesis that disease alters the acute physiological stress response. Whether the effects of ophidiomycosis on the acute stress response result in sublethal effects on fitness should be investigated in future studies.

Environmental conditions of recognition memory testing induce neurovascular changes in the hippocampus in a sex-specific manner in mice

Experiences are linked to emotions impacting memory consolidation and associated brain neuronal circuits. Posttraumatic stress disorder is an example of strong negative emotions affecting memory processes by flashbacks of past traumas. Stress-related memory deficits are also observed in major depressive disorder (MDD). We recently highlighted that sex-specific blood-brain barrier (BBB) alterations underlie stress responses in mice and human depression. However, little is known about the relationship between emotional valence, memory encoding and BBB gene expression. Here, we investigated the effects of novel object recognition (NOR) test, an experience considered of neutral emotional valence, on BBB properties in dorsal vs ventral hippocampus (HIPP) in the context of various environmental conditions (arena size, handling, age). The HIPP is a brain area central for learning and memory processes with the dorsal and ventral subregions being associated with working memory vs reference memory retrieval, respectively. Expression of genes related to BBB integrity are altered in line with learning and memory processes in a region- and sex-specific manner. We observed correlations between poor learning, anxiety, stress-induced corticosterone release and changes in BBB-associated gene expression. Comparison of BBB transcriptomes between sexes also revealed profound differences at baseline in both ventral and dorsal HIPP. Finally, we identified circulating vascular biomarkers, such as sE-selectin and matrix metallopeptidase 9 (MMP-9), altered following NOR exposure supporting that recognition memory formation has an impact on the neurovasculature. Although deemed as a neutral valence test, NOR experimental conditions can shift it toward a negative valence, impacting performance and highlighting the need to minimize anxiety when performing this commonly used test in mice.

Baseline corticosterone levels in spadefoot toads reflect alternate larval diets one year later

Early-life environmental variation can influence later-life physiology, such as the regulation of glucocorticoids. However, characterizing the effects of environmental factors on hormone regulation can be hampered when assessing animals that are small and require destructive sampling to collect blood. Using spadefoot toads (genus Spea), we evaluated whether waterborne corticosterone (CORT) measures could be used as a proxy for plasma CORT measures, detect stress-induced levels of CORT, and detect larval diet-induced changes in CORT regulation after metamorphosed individuals were maintained for 1 year under common garden conditions. We found that waterborne CORT measures were correlated with plasma CORT measures and could be used to detect stress-induced levels of CORT. Further, larval diet type significantly influenced baseline plasma CORT levels 1-year post-metamorphosis: adults that had consumed live prey as larvae had higher plasma CORT levels than adults that had consumed detritus as larvae. However, waterborne measures failed to reflect these differences, possibly due to low sample size. Our study demonstrates the utility of the waterborne hormone assay in assessing variation in baseline and stress-induced CORT levels in adult spadefoots. However, resolving more subtle differences that arise through developmental plasticity will require larger samples sizes when using the waterborne assay.

Perspectives on environmental heterogeneity and seasonal modulation of stress response in neotropical birds

Corticosterone (CORT), the main glucocorticoid in birds, regulates physiological and behavioral traits linked to predictable and unpredictable environmental fluctuations (i.e., stressors). Baseline and stress-induced CORT concentrations are known to fluctuate seasonally, linked to life history stages (LHS) such as breeding, molt, and wintering stage. These variations have been relatively well described in North American birds, but poorly addressed in neotropical species. To fill this gap, we explored how baseline and stress-induced CORT variation by LHS was affected by seasonality and environmental heterogeneity (i.e., frequency of unpredictable events such as droughts, flashfloods, etc) within the Neotropics using two approaches. First, we reviewed all currently available data about CORT concentrations for neotropical bird species. Second, we performed an in-depth analysis comparing the CORT responses of the two most common species of the Zonotrichia genus from North and South America (Z. leucophrys and Z. capensis, respectively) and their subspecies to seasonality and environmental heterogeneity. These species have been analyzed with the same methodology, allowing for an in-depth comparison of CORT variations. Despite scant data on neotropical bird species, we observed overlap between molt and breeding, and lower fluctuations of CORT among LHS. These patterns would be considered atypical compared to those described for North temperate species. Further, we found no significant associations between environmental heterogeneity and the stress-responses. In Zonotrichia we observed a positive association between baseline and stress-induced concentrations of CORT and latitude. We also observed differences by LHS. Both baseline and stress-induced CORT concentrations were higher during breeding and lower during molt. In addition, for both species, the overall pattern of seasonal modulation of stress response was heavily influenced by the migration strategy, with long-distance migrants showing significantly higher stress-induced CORT levels. Our results highlight the need for more data collection in the Neotropics. Comparative data would shed further light on the sensitivity of the adrenocortical response to stress under different scenarios of environmental seasonality and unpredictability.

Physiological but not morphological adjustments along latitudinal gradients in a human commensal species, the Eurasian tree sparrow.

Human commensal species take advantage of anthropogenic conditions that are less likely to be challenged by the selective pressures of natural environments. Their morphological and physiological phenotypes can therefore dissociate from habitat characteristics. Understanding how these species adjust their morphological and physiological traits across latitudinal gradients is fundamental to uncovering the eco-physiological strategies underlying coping mechanisms. Here, we studied morphological traits in breeding Eurasian tree sparrows (ETSs; Passer montanus) among low-latitude (Yunnan and Hunan) and middle-latitude (Hebei) localities in China. We then compared body mass, lengths of bill, tarsometatarsus, wing, total body, and tail feather, baseline and capture stress-induced levels of plasma corticosterone (CORT) and the metabolites including glucose (Glu), total triglyceride (TG), free fatty acid (FFA), total protein (TP), and uric acid (UA). None of the measured morphological parameters varied with latitude except in the Hunan population, which demonstrated longer bills than those in other populations. Stress-induced CORT levels significantly exceeded baseline levels and decreased with increasing latitude, but total integrated CORT levels did not vary with latitude. Capture stress induced significantly increased Glu levels and decreased TG levels, independent of site. However, the Hunan population had significantly higher baseline CORT, baseline and stress-induced FFA levels but lower UA levels, which differed from other populations. Our results suggest that rather than morphological adjustments, physiological adjustments are mainly involved in coping mechanisms for middle-latitude adaptation in ETSs. It is worth investigating whether other avian species also exhibit such dissociation from external morphological designs while depending on physiological adjustments. This article is protected by copyright. All rights reserved.

Male Stressed Mice Having Behavioral Control Exhibit Escalations in Dorsal Dentate Adult-Born Neurons and Spatial Memory.

An escapable (ES)/inescapable stress (IS) paradigm was used to study whether behavioral control and repeated footshock stressors may affect adult neurogenesis and related cognitive function. Male stressed mice having behavioral control (ES) had a short-term escalation in dorsal dentate gyrus (DG) neurogenesis, while similarly stressed mice having no such control had unaltered neurogenesis as compared to control mice receiving no stressors. Paradoxically, ES and IS mice had comparable stress-induced corticosterone elevations throughout the stress regimen. Appetitive operant conditioning and forced running procedures were used to model learning and exercise effects in this escapable/inescapable paradigm. Further, conditioning and running procedures did not seem to affect the mice's corticosterone or short-term neurogenesis. ES and IS mice did not show noticeable long-term changes in their dorsal DG neurogenesis, gliogenesis, local neuronal density, apoptosis, autophagic flux, or heterotypic stress responses. ES mice were found to have a greater number of previously labeled and functionally integrated DG neurons as compared to IS and control mice 6 weeks after the conclusion of the stressor regimen. Likewise, ES mice outperformed IS and non-stressed control mice for the first two, but not the remaining two, trials in the object location task. Compared to non-stressed controls, temozolomide-treated ES and IS mice having a lower number of dorsal DG 6-week-old neurons display poor performance in their object location working memory. These results, taken together, prompt us to conclude that repeated stressors, albeit their corticosterone secretion-stimulating effect, do not necessary affect adult dorsal DG neurogenesis. Moreover, stressed animals having behavioral control may display adult neurogenesis escalation in the dorsal DG. Furthermore, the number of 6-week-old and functionally-integrated neurons in the dorsal DG seems to confer the quality of spatial location working memory. Finally, these 6-week-old, adult-born neurons seem to contribute spatial location memory in a use-dependent manner.

The resilience of adolescent male rats to acute stress-induced delayed anxiety is age-related and glucocorticoid release-dependent

Studies investigated how stressful experiences modulate physiological and behavioral responses and the consequences of stress-induced corticosterone release in anxiety-like behavior. Adolescence is crucial to brain maturation, and several neurobiological changes in this period lead individuals to increased susceptibility or resilience to aversive situations. Despite the effects of stress in adults, information about adolescents' responses to acute stress is lacking. We aimed to understand how adolescence affects acute stress responses. Male adolescent rats (30 days old) were 2 h restrained, and anxiety-like behaviors were measured immediately or 10 days after stress in the elevated plus-maze (EPM) and the light-dark box (LDB) tests. To verify the importance of CORT modulation in stress-induced anxiety, another group of rats was treated, 30 min before restraint, with metyrapone to blunt the stress-induced CORT peak and tested immediately after stress. To show that stress effects on behavior were age-dependent, another set of rats was tested in two different periods – early adolescence (30 days old) and mid-adolescence (40 days old) and were treated or not with metyrapone before the stress session and tested immediately or ten days later in the LDB test. Only early adolescent male rats were resilient to delayed anxiety-like behavior in EPM and LDB tests. Metyrapone treatment increased the rats' exploration immediately and ten days after stress. These data suggest a specific age at which adolescent rats are resilient to the delayed effects of acute restraint stress and that the metyrapone treatment has long-term behavioral consequences.

Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress

Introduction: Accumulating evidence indicates that abnormalities in the composition of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. Methods and Results: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compositions in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent experiments, we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 weeks attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. Conclusions: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.

Prior parental experience attenuates hormonal stress responses and alters hippocampal glucocorticoid receptors in biparental rock doves.

In the face of challenges, animals must balance investments in reproductive effort versus their own survival. Physiologically, this tradeoff may be mediated by glucocorticoid release by the hypothalamic-pituitary-adrenal (HPA) axis and prolactin release from the pituitary to maintain parental care. The degree to which animals react to and recover from stressors likely affects maintenance of parental behavior and ultimately, fitness. However, less is known about how gaining parental experience may alter hormonal stress responses and their underlying neuroendocrine mechanisms. To address this gap, we measured the corticosterone (CORT) and prolactin (PRL) stress response in both sexes of the biparental rock dove (Columba livia) that had never raised chicks versus birds that had fledged at least one chick. We measured both CORT and PRL at baseline and after an acute stressor (30 minutes restraint). We also measured negative feedback ability by administering dexamethasone, a synthetic glucocorticoid that suppresses CORT release, and measured CORT and PRL after 60 minutes. All hormones we measured when birds were not actively nesting to assess whether effects of parental experience extend beyond the breeding bout. Experienced birds had lower stress-induced and negative-feedback CORT, and higher stress-induced PRL than inexperienced birds. In a separate experiment, we measured glucocorticoid receptor subtype expression in the hippocampus, a key site of negative feedback regulation. Experienced birds expressed higher glucocorticoid receptors than inexperienced controls, which may mediate their ability to attenuate CORT release. Together, these results shed light on potential mechanisms by which gaining experience may improve parental performance and fitness.

Among-species variation in hormone concentrations is associated with urban tolerance in birds.

As cities expand across the globe, understanding factors that underlie variation in urban tolerance is vital for predicting changes in patterns of biodiversity. Endocrine traits, like circulating hormone concentrations and regulation of endocrine responses, might contribute to variation in species' ability to cope with urban challenges. For example, variation in glucocorticoid and androgen concentrations has been linked to life-history and behavioural traits that are associated with urban tolerance. However, we lack an understanding of the degree to which evolved differences in endocrine traits predict variation in urban tolerance across species. We analysed 1391 estimates of circulating baseline corticosterone, stress-induced corticosterone, and testosterone concentrations paired with citizen-science-derived urban occurrence scores in a broad comparative analysis of endocrine phenotypes across 71 bird species that differ in their occurrence in urban habitats. Our results reveal context-dependent links between baseline corticosterone and urban tolerance, as well as testosterone and urban tolerance. Stress-induced corticosterone was not related to urban tolerance. These findings suggest that some endocrine phenotypes contribute to a species' tolerance of urban habitats, but also indicate that other aspects of the endocrine phenotype, such as the ability to appropriately attenuate responses to urban challenges, might be important for success in cities.