Changes In Corticosterone Levels Research Articles

Ketamine alleviates PTSD-like effect and improves hippocampal synaptic plasticity via regulation of GSK-3β/GR signaling of rats

BackgroundEach year, 3–4% of the global population experiences post-traumatic stress disorder (PTSD), a chronic mental disorder with significant social and economic repercussions. Although it has been shown that ketamine can effectively alleviate PTSD symptoms in individuals, the specific mechanism of action underlying its anti-PTSD effects remains unclear. In this study, we investigated how a single, low dose of ketamine affected the glycogen synthase kinase 3β (GSK-3β)/glucocorticoid receptor (GR) signaling pathway in a single prolonged stress (SPS)-induced PTSD rat model. MethodsAfter establishing the model, stress-related behavioral alterations in the rats were assessed following intraperitoneal injections of ketamine (10 mg/kg) and GSK-3β antagonist SB216763 (5 mg/kg). In the hippocampus, alterations in the expression of specific proteins implicated in PTSD development, such as GR, brain-derived neurotrophic factor (BDNF), GSK-3β, and phosphorylated glycogen synthase kinase 3β (p-GSK-3β), were assessed. We also measured changes in the mRNA expression levels of GR, BDNF, GSK-3β, FK501 binding protein 51 (FKBP5), and corticotropin-releasing hormone (CRH), as well as synaptic ultrastructure, in the hippocampus, and measured changes in corticosterone levels in the blood. ResultsSPS induced anxiety-like and depression-like behaviors in rats and induced morphological changes in synapse, which were accompanied by higher GSK-3β protein expression and conversely, decreased expression of GR, BDNF, p-GSK-3β, FKBP5 and CRH. Intraperitoneal administration of ketamine (10 mg/kg) after SPS prevented SPS-induced anxiety-like behaviors. Most importantly, ketamine attenuated SPS-induced dysfunctions in GSK-3β/GR signaling and synaptic deficits. Furthermore, treatment with a GSK-3β inhibitor played the same effect as ketamine on behavioral changes of SPS model rats. ConclusionSingle doses of ketamine effectively ameliorate SPS-induced anxiety-like symptoms, potentially by improving synaptic plastic in the hippocampus by regulating GSK-3β/GR signaling.

Diosgenin normalization of disrupted behavioral and central neurochemical activity after single prolonged stress.

Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice. Methodology: SPS was induced by restraining animals for 2h, followed by 20min of forced swim, recuperation for 15min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels. Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice. Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD.

40 Hz Light Flicker Promotes Learning and Memory via Long Term Depression in Wild-Type Mice.

40 Hz light flicker is a well-known non-invasive treatment that is thought to be effective in treating Alzheimer's disease. However, the effects of 40 Hz visual stimulation on neural networks, synaptic plasticity, and learning and memory in wild-type animals remain unclear. We aimed to explore the impact of 40 Hz visual stimulation on synaptic plasticity, place cell, and learning and memory in wild-type mice. c-Fos+ cell distribution and in vivo electrophysiology was used to explore the effects of 40 Hz chronic visual stimulation on neural networks and neuroplasticity in wild-type mice. The character of c-Fos+ distribution in the brain and the changes of corticosterone levels in the blood were used to investigate the state of animal. Place cell analysis and novel location test were utilized to examine the effects of 40 Hz chronic visual stimulation on learning and memory in wild-type mice. We found that 40 Hz light flicker significantly affected many brain regions that are related to stress. Also, 40 Hz induced gamma enrichment within 15 min after light flickers and impaired the expression of long-term potentiation (LTP), while facilitated the expression of long-term depression (LTD) in the hippocampal CA1. Furthermore, 40 Hz light flicker enhanced the expression of corticosterone, rendered well-formed place cells unstable and improved animal's learning and memory in novel local recognition test, which could be blocked by pre-treatment with the LTD specific blocker Glu2A-3Y. These finding suggested that 40 Hz chronic light flicker contains stress effects, promoting learning and memory in wild-type mice via LTD.

Age and Parity Effects in the Hypothalamic Pituitary Adrenal Axis’ Response to Multimodal Stress in Female Mice

The hypothalamic pituitary adrenal (HPA) axis responds to environmental perturbations to maintain homeostasis. Pregnancy demands extensive modifications in HPA axis function to prepare for increased energy and metabolic demands required to meet the needs of mother and offspring. Short-term effects of pregnancy on the HPA axis have been shown, but data is lacking regarding the long-term effects in middle-aged female mice no longer breeding. Since changes of the HPA axis are further found with age, in this study, we examined both parity- and age-related interactions on the HPA axis in female mice. Wildtype C57bl/6N females were divided into nulliparous young (NY) (3-6 mo) and nulliparous middle-aged (NM) or multiparous retired-breeder middle-aged (RBM) (8-10 mo) groups. RBM mice were killed at least 4 weeks after their last litter was weaned. Control mice were euthanized directly out of the home cage and experimental groups were euthanized at 0 min, 30 min, or 90 min recovery (n=8-10/ group) after 2h of multi-modal stress (MMS; restraint, noise, shaker, light). (Paraventricular nucleus of the hypothalamus (PVN) neuronal activity was quantified by c-FOS immunoreactivity (-ir), and plasma corticosterone (CORT) levels were measured by radioimmunoassay. Corticotropin releasing hormone (CRH) mRNA was assayed by in situ hybridization. Two-way ANOVA showed effects of age (p<0.0248), parity (p<0.0021), time (p<0.0001), and interaction (p<0.0009) on CORT levels. Specifically, basal CORT levels were reduced in NM/RBM versus NY mice. In all groups, CORT levels were significantly elevated by MMS. There was no difference between CORT levels immediately after MMS in NY or NM groups, but CORT levels after 30- and 90- min recovery from MMS remained elevated in NM, indicating reduced negative feedback with age. Additionally, RBM plasma CORT was further reduced in all time groups versus NM, accompanied by a return to baseline CORT after 90 min recovery, suggesting a parity-dependent effect on the HPA axis. Changes in CORT levels were correlated with c-FOS-ir. MMS increased PVN c-FOS-ir in all groups compared to controls and c-FOS-ir in NM was significantly greater than PVN c-FOS of RBM. Further, while c-FOS-ir in the NY females was reduced to baseline 30 min after MMS, the return to baseline was more gradual in NM. No effect of parity or age was seen in Crh mRNA. Collectively, our findings show that activation of the HPA axis in females involves interactions between age- and parity- dependent function. Our findings further show activation and inhibition of the HPA axis in females involving long-term changes that occur after pregnancy, which may increase risk for stress- or postpartum- related disorders. Supported by NIDDK 1-R01 DK105826

OR19-03 Effects of Nonpeptide Orally Bioavailable ACTH Antagonists on Adrenal Gland Size and Function in Rats

Cushing’s disease (CD) and Ectopic ACTH syndrome (EAS) stem from excess circulating adrenocorticotropic hormone (ACTH) and resulting hypercortisolemia. In CD, excess ACTH is secreted from pituitary tumors, whereas excess ACTH in EAS arises from nonpituitary tumors. ACTH acts on the adrenal melanocortin type 2 (MC2) receptor to control the synthesis and secretion of adrenal hormones, including the stress hormone cortisol (corticosterone in rats) which accounts for the comorbidities of CD and EAS. Availability of a potent ACTH antagonist that can normalize cortisol in patients with diseases of excess ACTH will be a major advance in endocrinology. Additionally, an ACTH antagonist will have utility in congenital adrenal hyperplasia (CAH) because of its ability to block production of excess adrenal androgens.Crinetics is evaluating and developing ACTH antagonists for the treatment of diseases of excess ACTH. To our knowledge, these compounds represent the first potent nonpeptide ACTH antagonists to demonstrate in vitro potency and in vivo efficacy. As a result, the direct effects of sustained MC2 receptor blockade on the structure and function of the adrenal gland have never been able to be assessed. We examined the effects of several orally bioavailable ACTH antagonists across a range of doses on Sprague-Dawley rat adrenal gland weight, histology, and hormone levels in repeat dosing (7-14 days) studies. Sustained MC2 receptor antagonism dose dependently blocked activity of ACTH at the level of the adrenal gland and reduced plasma corticosterone levels. In the normal rat, this resulted in dose-dependent atrophy of the adrenal gland as assessed by organ weights and microscopically. The atrophy was primarily observed in the cortisol producing zona fasciculata, as well as in the zona reticularis, with smaller reductions noted in the aldosterone producing zona glomerulosa. Additionally, hypertrophy of the adrenal glands caused by continuous subcutaneous administration of exogenous ACTH was reversed by treatment with an ACTH antagonist. The adrenal effects were accompanied by expected changes in corticosterone levels. These preclinical findings demonstrate the therapeutic potential of ACTH antagonism and provide a strong rationale for development of an orally bioavailable drug that can be used to combat CD, EAS, and CAH.

LPA1 receptor and chronic stress: Effects on behaviour and the genes involved in the hippocampal excitatory/inhibitory balance

The LPA1 receptor, one of the six characterized G protein-coupled receptors (LPA1–6) through which lysophosphatidic acid acts, is likely involved in promoting normal emotional behaviours. Current data suggest that the LPA-LPA1-receptor pathway may be involved in mediating the negative consequences of stress on hippocampal function. However, to date, there is no available information regarding the mechanisms whereby the LPA1 receptor mediates this adaptation. To gain further insight into how the LPA-LPA1 pathway may prevent the negative consequences of chronic stress, we assessed the effects of the continuous delivery of LPA on depressive-like behaviours induced by a chronic restraint stress protocol. Because a proper excitatory/inhibitory balance seems to be key for controlling the stress response system, the gene expression of molecular markers of excitatory and inhibitory neurotransmission was also determined. In addition, the hippocampal expression of mineralocorticoid receptor genes and glucocorticoid receptor genes and proteins as well as plasma corticosterone levels were determined. Contrary to our expectations, the continuous delivery of LPA in chronically stressed animals potentiated rather than inhibited some (e.g., anhedonia, reduced latency to the first immobility period), though not all, behavioural effects of stress. Furthermore, this treatment led to an alteration in the genes coding for proteins involved in the excitatory/inhibitory balance in the ventral hippocampus and to changes in corticosterone levels. In conclusion, the results of this study reinforce the assumption that LPA is involved in emotional regulation, mainly through the LPA1 receptor, and regulates the effects of stress on hippocampal gene expression and hippocampus-dependent behaviour.

Anxiolytic and panicolytic-like effects of environmental enrichment seem to be modulated by serotonin neurons located in the dorsal subnucleus of the dorsal raphe

In a previous study, we showed that exposure of rats to a one-week environmental enrichment (EE) protocol decreases elevated T-maze (ETM) avoidance responses, an anxiolytic-like effect, without altering escape reactions, in clinical terms related to panic disorder. These anxiolytic-like effects were followed by decreased delta FosB-immunoreactivity (delta FosB-ir) in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. The purpose of the present study was to further investigate behavioral and neurophysiological alterations induced by EE exposure. For that, in a first experiment we verified if increasing the time of exposure to the same EE protocol used in our previous study (from one to two weeks) altered male Wistar rats’ ETM escape responses. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Since anxiety and panic-related reactions have been associated to the functioning of specific subnuclei of the dorsal raphe nucleus (DR), we also evaluated delta FosB-ir in serotonergic cells of DR regions. At last, we analyzed plasma corticosterone levels in animals submitted to EE and to standard housing. Results showed that a two-week exposure to EE decreases both ETM avoidance and escape reactions, inducing anxiolytic and panicolytic-like effects, respectively. There was also a significant decrease in the number of double staining neurons in the midrostral region of the dorsal subnucleus of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety and panic-related responses.

Chronic high corticosterone with voluntary corn oil ingestion induces significant body weight gain in mice

Corticosterone (CORT) is a powerful regulator of energy metabolism, and chronically high CORT levels cause obesity and diabetes in mice. It is reported that a chronically high CORT level changes food preference, increasing the intake of comfort foods such as fatty foods. Previously, we demonstrated that unlike a high fat diet, voluntary ingestion of 100% pure corn oil increased energy expenditure and thermogenesis through the activation of the interscapular brown adipose tissue (IBAT). In the present study, we investigated whether chronically high CORT affected corn oil intake, energy expenditure, and body weight gain. We delivered CORT to mice via water bottles and placed corn oil in a separate drinking bottle in the home cage. Voluntary corn oil ingestion with CORT induced significant body weight gain, while corn oil ingestion or CORT alone had a modest effect. CORT increased corn oil intake without reducing chow intake, which further increased the total daily caloric intake. CORT suppressed mRNA related to thermogenesis in IBAT. In the hypothalamus, CORT upregulated mRNA expression of the orexigenic neuropeptide, agouti-related protein. These data suggest that chronically high CORT might increase the desire to consume dietary fat, suppressing BAT function, thereby causing obesity.

Infradian Rhythms of Resistance to a Dissociative Anesthetic in Wistar Male Rats under Normal Conditions and After Surgical Removal of the Adrenal Glands and Testes.

Daily dynamics of changes in the latency of a response to dissociative anesthetic tiletamine (time from injection to ataxia) was studied in mature Wistar rats. Both intramuscular and intravenous administration of the anesthetic was associated with 4-day oscillations of the latent period synchronous with the dynamics of changes in the concentration of glucocorticoid hormones. The period and phases of the infradian rhythm of resistance to the anesthetic remained unchanged after removal of both adrenal glands and testes and administration of corticosterone synthesis blocker trilostane diminishing the 4-day cycle of changes in corticosterone level. Therefore, hormones of the adrenal glands and testes do not play the key role in the mechanisms of formation of the 4-day infradian rhythm.

Glucocorticoid response to both predictable and unpredictable challenges detected as corticosterone metabolites in collared flycatcher droppings.

In most vertebrate animals, glucocorticoid hormones are the chief mediators of homeostasis in response to ecological conditions and as they progress through their lifecycle. In addition, glucocorticoids are a major part of the stress response and stress induced elevations of the hormone can make it difficult to assess glucocorticoid secretion in response to changes in life-stage and current environmental conditions in wild animals. Particularly when quantifying circulating levels of glucocorticoids in the blood which fluctuate rapidly in response to stress. An alternative method of quantifying glucocorticoids is as hormone metabolites in faeces or urine giving a historical sample related to the gut passage time and urinary tract that is less sensitive to stressful events which cause spikes in the circulating hormone level. Although the concentration of glucocorticoid metabolites are influenced by faecal mass thereby potentially affecting any differences in hormone metabolites detected amongst samples. In the present study, we aimed to detect changes in levels of corticosterone, the primary bird glucocorticoid, in relation to the phase of reproduction, in a breeding population of collared flycatchers by sampling corticosterone metabolites in droppings. We also tested how corticosterone metabolite concentrations were affected by ambient temperature and related to body condition in adult birds. Our results indicate that the upregulation of corticosterone between incubation and nestling feeding in female birds is crucial for successful reproduction in this species. Also, females appear to downregulate corticosterone during incubation in response to lower ambient temperature and poorer body condition. Our results did not indicate a relationship between dropping mass and corticosterone metabolite concentrations, which suggests that our findings were linked to the regulation of corticosterone in response to predictable and unpredictable challenges.

Exploring the mechanistic link between corticosterone and insulin-like growth factor-1 in a wild passerine bird

BackgroundPhysiological regulators of life history trade-offs need to be responsive to sudden changes of resource availability. When homeostasis is challenged by unpredictable stressors, vertebrates respond through a set of physiological reactions, which can promote organismal survival. Glucocorticoids have been traditionally recognized as one of the main regulators of the physiological stress response, but the role of an evolutionarily more conserved pathway, the hypothalamic-pituitary-somatotropic (HPS) axis producing insulin-like growth factor-1 (IGF-1) has received much less attention. Although IGF-1 is known to affect several life history traits, little is known about its role in the physiological stress response and it has never been studied directly in adult wild animals.MethodsIn this study, we combined field observations with a controlled experiment to investigate how circulating levels of IGF-1 change in response to stress and whether this change is due to concomitant change in glucocorticoids in a free-living songbird, the bearded reedling Panurus biarmicus. We used a standard capture-restraint protocol in field observation, in which we took first and second (stress induced: 15 minutes later) samples. In a follow-up experiment, we used a minimally invasive oral corticosterone manipulation.ResultsWe showed that corticosterone levels significantly increased while IGF-1 levels significantly decreased during capture and handling stress. However, change in corticosterone levels were not related to change in IGF-1 levels. We found that experimentally elevated corticosterone levels did not affect IGF-1 levels.DiscussionOur results are the first to highlight that circulating IGF-1 levels are responsive to stress independently from glucocorticoids and suggest that the HPS axis is an autonomous physiological pathway that may play an important role as regulator of life-history decisions.

Chronic stress changes prepulse inhibition after amphetamine challenge: the role of the dopaminergic system.

The goal of this research was to examine the influence of chronic mild stress (CMS) on prepulse inhibition (PPI). We used an amphetamine challenge to study the role of the dopaminergic system in limbic structures. Chronic stress caused a reduction in both sucrose preference and body weight. It was found that the initially strong response to amphetamine in the control rats was weakened after stress on both the behavioural and biochemical levels: improved PPI, decreased dopamine D2 receptor expression in the central nucleus of amygdala (CeA) and nucleus accumbens (NAC), and decreased dopamine and 3-MT (3-methoxytyramine) levels in NAC. We observed that the stress-evoked attenuation of amphetamine-induced stimulation was also paralleled by changes in corticosterone level. These effects were accompanied by a decrease in both glutamate and the glutamate/gamma-aminobutric acid (GABA) ratio in the NAC. The interpretation of these results is that prolonged stress induces compensatory mechanisms in the mesolimbic system which are responsible for psychostimulant (amphetamine) effects.

Reduction in baseline corticosterone secretion correlates with climate warming and drying across wild lizard populations.

Climate change should lead to massive loss of biodiversity in most taxa, but the detailed physiological mechanisms underlying population extinction remain largely elusive so far. In vertebrates, baseline levels of hormones such as glucocorticoids (GCs) may be indicators of population state as their secretion to chronic stress can impair survival and reproduction. However, the relationship between GC secretion, climate change and population extinction risk remains unclear. In this study, we investigated whether levels of baseline corticosterone (the main GCs in reptiles) correlate with environmental conditions and associated extinction risk across wild populations of the common lizard Zootoca vivipara. First, we performed a cross-sectional comparison of baseline corticosterone levels along an altitudinal gradient among 14 populations. Then, we used a longitudinal study in eight populations to examine the changes in corticosterone levels following the exposure to a heatwave period. Unexpectedly, baseline corticosterone decreased with increasing thermal conditions at rest in females and was not correlated with extinction risk. In addition, baseline corticosterone levels decreased after exposure to an extreme heatwave period. This seasonal corticosterone decrease was more pronounced in populations without access to standing water. We suggest that low basal secretion of corticosterone may entail downregulating activity levels and limit exposure to adverse climatic conditions, especially to reduce water loss. These new insights suggest that rapid population decline might be preceded by a downregulation of the corticosterone secretion.

Environmental enrichment decreases avoidance responses in the elevated T-maze and delta FosB immunoreactivity in anxiety-related brain regions

Environmental enrichment (EE) is an animal management technique, which seems to improve adaptation to the experimental conditions of housing in laboratory animals. Previous studies have pointed to different beneficial effects of the procedure in the treatment of several disorders, including psychiatric conditions such as depression. The anxiolytic effects induced by EE, on the other hand, are not as clear. In fact, it has been proposed that EE acts as a mild stressor agent. To better understand the relationship of EE with anxiety-related responses, the present study exposed rats to one week of EE and subsequently tested these animals in the inhibitory avoidance and escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Additionally, analysis of delta FosB protein immunoreactivity (FosB-ir) was used to map areas activated by EE exposure and plasma corticosterone measurements were performed. The results obtained demonstrate that exposure to EE for one week impaired avoidance responses, an anxiolytic-like effect, without altering escape reactions. Also, in animals submitted to the avoidance task EE exposure decreased FosB-ir in the cingulate cortex, dorsolateral and intermediate lateral septum, hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and basolateral amygdala and ventral region of the dorsal raphe nucleus. Although no behavioral differences were observed in animals submitted to the escape task, EE exposure also decreased FosB-ir in the cingulate cortex, hippocampus (dentate gyrus), lateral amygdala, paraventricular, anterior and ventromedial hypothalamus, dorsomedial periaqueductal gray and ventral and dorsal region of the dorsal raphe. No changes in corticosterone levels, however, were observed. These results contribute to a better understanding of the effects of EE on anxiety.

A marker of biological age explains individual variation in the strength of the adult stress response.

The acute stress response functions to prioritize behavioural and physiological processes that maximize survival in the face of immediate threat. There is variation between individuals in the strength of the adult stress response that is of interest in both evolutionary biology and medicine. Age is an established source of this variation—stress responsiveness diminishes with increasing age in a range of species—but unexplained variation remains. Since individuals of the same chronological age may differ markedly in their pace of biological ageing, we asked whether biological age—measured here via erythrocyte telomere length—predicts variation in stress responsiveness in adult animals of the same chronological age. We studied two cohorts of European starlings in which we had previously manipulated the rate of biological ageing by experimentally altering the competition experienced by chicks in the fortnight following hatching. We predicted that individuals with greater developmental telomere attrition, and hence greater biological age, would show an attenuated corticosterone (CORT) response to an acute stressor when tested as adults. In both cohorts, we found that birds with greater developmental telomere attrition had lower peak CORT levels and a more negative change in CORT levels between 15 and 30 min following stress exposure. Our results, therefore, provide strong evidence that a measure of biological age explains individual variation in stress responsiveness: birds that were biologically older were less stress responsive. Our results provide a novel explanation for the phenomenon of developmental programming of the stress response: observed changes in stress physiology as a result of exposure to early-life adversity may reflect changes in ageing.

Elevated levels of the stress hormone, corticosterone, cause \u2018pessimistic\u2019 judgment bias in broiler chickens

Pessimistic judgment biases, whereby humans or non-human animals interpret ambiguous information negatively, are hypothesised to be one of the suite of adaptive changes that comprise the vertebrate stress response. To test this hypothesis, we asked whether experimentally elevating levels of the glucocorticoid stress hormone, corticosterone, in broiler chickens produced a pessimistic judgment bias. We trained young chickens to discriminate a stimulus (paper cone) placed at two locations in an arena, one associated with reward (mealworms) and one with punishment (air puff). During seven days of non-invasive administration of either corticosterone or vehicle control, we tested the birds’ responses to the cone placed at ambiguous locations between the trained locations. Corticosterone-treated birds were more likely than controls to respond as if punishment was likely when the cone was placed near to the punished location. The degree of this ‘pessimism’ was associated with smaller relative spleen weight, which is a documented consequence of chronic stress in chickens. We conclude that changes in corticosterone levels in chickens are sufficient to cause a specific change in decision making, dubbed ‘pessimism’, whereby corticosterone-treated birds showed an increased expectation of punishment in the face of ambiguous information. Pessimism could be a useful welfare indicator in chickens.

Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels

Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress’ effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic management of stress-related cognitive deficits.

Hippocampal BDNF in physiological conditions and social isolation

Exposure of an organism to chronic psychosocial stress may affect brain-derived neurotrophic factor (BDNF) expression that has been implicated in the etiology of psychiatric disorders, such as depression. Given that depression in humans has been linked with social stress, the chronic social stress paradigms for modeling psychiatric disorders in animals have thus been developed. Chronic social isolation in animal models generally causes changes in hypothalamic-pituitary-adrenal axis functioning, associated with anxiety- and depressive-like behaviors. Also, this chronic stress causes downregulation of BDNF protein and mRNA in the hippocampus, a stress-sensitive brain region closely related to the pathophysiology of depression. In this review, we discuss the current knowledge regarding the structure, function, intracellular signaling, inter-individual differences and epigenetic regulation of BDNF in both physiological conditions and depression and changes in corticosterone levels, as a marker of stress response. Since BDNF levels are age dependent in humans and rodents, this review will also highlight the effects of adolescent and adult chronic social isolation models of both genders on the BDNF expression.

Habitat degradation increases stress-hormone levels during the breeding season, and decreases survival and reproduction in adult common lizards.

The allostatic load model describes how individuals maintain homeostasis in challenging environment and posits that costs induced by a chronic perturbation (i.e., allostatic load) are correlated to the secretion of glucocorticoids, such as corticosterone. Habitat perturbations from anthropogenic activities are multiple and functional responses to those are still unclear. Here, we manipulated the habitat quality in 24 semi-natural populations of the common lizard during 1year. We tested the predictions of the allostatic load model that habitat degradation should increase baseline corticosterone levels, and should induce concomitant physiological changes, such as lipid mobilization and lower immunocompetence, and demographic changes, such as lower body growth, survival and/or reproductive performances. Our results highlight stage-dependent effects of habitat degradation on physiological traits during the breeding season: adult lizards had higher baseline corticosterone levels and yearling lizards had a lower inflammatory response than adults, whereas juveniles had higher circulating lipid levels than yearlings and adults without concomitant change in corticosterone levels. In addition, habitat degradation reduced the performances of adults but not of juveniles: in low habitat quality populations, adult males had a lower survival and females had a smaller fecundity. These results are in accordance with the allostatic load model given that allostatic load was detected only during the season and in life stages of maximal energy expenditure. This underlines the importance to account for individual energy requirements to better understand demographic responses to habitat perturbation.

Upregulation of Mineralocorticoid Receptor in the Hypothalamus Associated with a High Anxiety-like Level in Apolipoprotein E4 Transgenic Mice.

Anxiety symptoms occur in a large portion of Alzheimer's disease (AD) patients. ApolipoproteinE-4 (ApoE ε4 allele), a risk factor for AD, has been recognized as an important contributor to psychiatric disorders. In the present study, we aimed to investigate the corticosterone level in relation to anxiety-like behavior changes in transgenic male mice with different glial fibrillary acidic protein (GFAP)-ApoE isoforms. GFAP-ApoE4 transgenic mice aged 3months showed higher anxiety-like behavior in open field, light-dark box and elevated plus maze tasks compared with that of age-matched GFAP-ApoE3 mice. However, corticotropin releasing factor levels in the hypothalamus and plasma corticosterone secretion were similar in GFAP-ApoE3 and GFAP-ApoE4 transgenic male mice. Additionally, increased expression of the mineralocorticoid receptor (MR) and unchanged expression of the glucocorticoid receptor were observed in the hypothalamus of GFAP-ApoE4 mice. However, no significant differences were found in the expression levels of the MR in GFAP-ApoE3 and GFAP-ApoE4 mice at postnatal day 2. In conclusion, we found that MR upregulation rather than corticosterone level changes in the early stage of adulthood was associated with the higher anxiety-like level measured in GFAP-ApoE4 mice.