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Stress can have severe psychological and physiological consequences. Thus, inappropriate regulation of the stress response is linked to the etiology of mood and anxiety disorders. The generation and implementation of preclinical animal models represent valuable tools to explore and characterize the mechanisms underlying the pathophysiology of stress-related psychiatric disorders and the development of novel pharmacological strategies. In this commentary, we discuss the strengths and limitations of state-of-the-art molecular and computational advances employed in stress neurobiology research, with a focus on the ever-increasing spatiotemporal resolution in cell biology and behavioral science. Finally, we share our perspective on future directions in the fields of preclinical and human stress research. [ABSTRACT FROM AUTHOR]

Stress can have severe psychological and physiological consequences. Thus, inappropriate regulation of the stress response is linked to the etiology of mood and anxiety disorders. The generation and implementation of preclinical animal models represent valuable tools to explore and characterize the mechanisms underlying the pathophysiology of stress-related psychiatric disorders and the development of novel pharmacological strategies. In this commentary, we discuss the strengths and limitations of state-of-the-art molecular and computational advances employed in stress neurobiology research, with a focus on the ever-increasing spatiotemporal resolution in cell biology and behavioral science. Finally, we share our perspective on future directions in the fields of preclinical and human stress research.

Purpose: Psychological stress could negatively influence female reproductive ability. d‐Leucine (d‐Leu) is a d‐type amino acid found in foods and mammalian tissues. We have examined the protective effects of d‐Leu on oocyte abnormality induced by psychological stress. Methods: Female mice (6‐week‐old) were divided into three groups: control, restraint stress (RS), and RS/d‐Leu. The RS and RS/d‐Leu mice were holed for 3 hours daily during 14 days. RS/d‐Leu mice were fed 0.3% d‐Leu diet. The oocyte maturation failure was analyzed by shapes of spindles and chromosomes. In addition, levels of heme‐oxygenase‐1 (HO‐1) and superoxide dismutase (SOD) expression in the ovaries were also examined. Whether d‐Leu reduces the generation of reactive oxygen species (ROS) in cultured cells, K562 cells were treated with d‐Leu, and then ROS in K562 were analyzed. Results: Oocyte maturation failure was increased in RS mice. d‐Leu reduced abnormal oocytes to control level. The expression levels of HO‐1 and SOD2 increased in RS/d‐Leu mice compared to those of RS mice. ROS levels were decreased in K562 cells with d‐Leu in a dose‐dependent manner. Conclusions: We concluded that d‐Leu protects oocytes from psychological stress through the induction of HO‐1 and SOD2 expression then by reducing oxidative stress. [ABSTRACT FROM AUTHOR]

Introduction. Stress during puberty exerts long-term effects on endocrine systems and brain structures, such as the prefrontal cortex (PFC) and basolateral amygdala (BLA), two cerebral areas that participate in modulating sexual behavior and whose functioning is regulated by androgenic hormones. Objective. To evaluate the effect of pubertal stress due to social isolation on the sexual motivation, serum testosterone levels, and electroencephalographic activity (EEG) of the PFC and BLA in male rats. Method. Sixty sexually-experienced male rats were used. Thirty were stressed by social isolation during puberty (SG, housed 1 per cage, postnatal days 25-50); the other 30 formed the control group (CG, 5 per cage). All rats were implanted bilaterally with stainless steel electrodes in the PFC and BLA. EEGs were recorded during the awake-quiet state in two conditions: without sexual motivation (WSM), and with sexual motivation (SM). After EEG recording, the rats were sacrificed by decapitation to measure their testosterone levels. Results. SG showed lower sexual motivation and testosterone levels, but higher amygdaline EEG activation in the presence of a receptive female, while CG showed higher prefrontal EEG activation. Discussion and conclusion. It is probable that the decreased testosterone levels resulting from pubertal stress affected prefrontal and amygdaline functionality and, hence, sexual motivation. These data could explain some of the hormonal and cerebral changes associated with stress-induced sexual alterations, though this suggestion requires additional clinical and animal research. [ABSTRACT FROM AUTHOR]

Mice are the preeminent research organism in which to model human diseases and study the involvement of the immune response. Rapidly accumulating evidence indicates a significant involvement of stress hormones in cancer progression, resistance to therapies, and suppression of immune responses. As a result, there has been a concerted effort to model human stress in mice. In this article, we discuss recent literature showing how mice in research facilities are chronically stressed at baseline because of environmental factors. Focusing on housing temperature, we suggest that the stress of cool housing temperatures contributes to the impact of other imposed experimental stressors and therefore has a confounding effect on mouse stress models. Furthermore, we propose that manipulation of housing temperature is a useful approach for studying the impact of chronic stress on disease and the immune response and for testing therapeutic methods of reducing the negative effects of chronic stress. [ABSTRACT FROM AUTHOR]

Highlights Somatic and neuroendocrine effects were independent of stress type and hypertension. Both rat strains presented vulnerability to cardiovascular effects of the homotypic stressor. Hypertensive animals were more vulnerable than normotensive rats to the cardiovascular effects. Abstract This study investigated neuroendocrine, autonomic, and cardiovascular changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in 60-days-old female normotensive Wistar rats and female spontaneously hypertensive rats (SHR). Both strains of rats were exposed for 10 consecutive days to either the homotypic stressor repeated restraint stress (RRS) or the heterotypic stressor chronic unpredictable stress (CUS). As expected, SHR had higher baseline blood pressure values and impaired baroreflex activity in relation to normotensive animals. Besides, SHR presented higher plasma corticosterone levels and decreased thymus weight. Both RRS and CUS increased baseline plasma corticosterone concentration and decreased body weight gain in both normotensive and SHR rats. In addition, both stress protocols caused hypertrophy of adrenal glands in normotensive rats. Regarding the cardiovascular effects, RRS increased basal heart rate in both rat strains, which was mediated by an increase in sympathetic tone to the heart. Besides, RRS increased baroreflex-mediated tachycardia in SHR animals, while CUS increased cardiac parasympathetic activity and pacemaker activity in normotensive rats. Taken together, these results indicate a stress type-specific effect, as identified by a vulnerability of both strains to the deleterious cardiovascular effects evoked by the homotypic stressor and a resilience to the impact of the heterotypic stressor. Vulnerability of hypertensive rats was evidenced by the absence of CUS-evoked adaptive cardiovascular responses and an increase of baroreflex tachycardia in SHR animals subjected to RRS. The somatic and HPA axis changes were overall independent of the chronic stress regimen and pre-existing hypertension. [ABSTRACT FROM AUTHOR]

Aging is associated with altered sleep architecture and worsened hippocampus-dependent cognition, highly prevalent clinical conditions that detract from quality of life for the elderly. Interestingly, exposure to psychosocial stress causes similar responses in young subjects, suggesting that age itself may act as a stressor. In prior work, we demonstrated that young animals show loss of deep sleep, deficits in cognition, and elevated body temperature after acute stress exposure, whereas aged animals are hyporesponsive on these measures. However, it is unclear if these age-altered stress responses occur in parallel over the course of aging. To address this, here we repeated the experiment in mid-aged animals. We hypothesized that mid-aged stress responses would be intermediate between those of young and aged subjects. Sixteen mid-aged (12 months) male F344 rats were implanted with EEG/EMG emitters to monitor sleep architecture and body temperature, and were trained on the Morris water maze for 3 days. On the fourth day, half of the subjects were restrained for 3 hours immediately before the water maze probe trial. Sleep architecture and body temperature were measured during the ensuing inactive period, and on the following day, endpoint measures were taken. Restrained mid-aged animals showed resistance to deep sleep loss, but demonstrated stress-induced water maze probe trial performance deficits as well as postrestraint hyperthermia. Taken in the context of prior work, these data suggest that age-related loss of sleep architecture stress sensitivity may precede both cognitive and body temperature–related stress insensitivity. [ABSTRACT FROM AUTHOR]

Highlights • Early life stress in mice is a unique model mimicking main IBS features. • Early life stress do not precipitate nor exacerbate colitis in mouse models genetically predisposed to IBD. • Early life stress do not increase susceptibility to gastrointestinal pathogen infections. • These results are consistent with epidemiological studies. Abstract Neonatal period is characterized by an immature intestinal barrier. Scattered evidence suggests that early life stressful events induce long lasting alterations of intestinal homeostasis mimicking Irritable Bowel Syndrome (IBS). Those observations highlighting defect of intestinal barrier by early life stress questioned its potential role as a risk factor for gastrointestinal disorders such as colitis and infections. In this study, we aimed to analyze if maternal separation (MS) in mice mimicks IBS main features. We next addressed whether MS could trigger or exacerbate colitis in genetically predisposed mice and/or enhance susceptibility to gastrointestinal infections in wild type mice. MS induced main features of IBS in adult wild type male mice i.e. intestinal hyperpermeability, visceral hypersensitivity, microbiota dysbiosis, bile acid malabsorption and low grade inflammation in intestine associated with a defect of Paneth cells and the ILC3 population. This breach in mucosal barrier functions in adults was associated with a systemic IgG response against commensal E. coli and increased IFNγ secretion by splenocytes. However, in IL10−/− mice, MS did not trigger nor worsen colitis. Furthermore, wild type mice submitted to MS did not show increase susceptibility to gastrointestinal infections (S. Typhimurium, L. monocytogenes or T. gondii) compared to controls. Altogether, our results identify MS in mice as a good experimental model for IBS mimicking all the main features. In addition, early life stress, even though it has long lasting consequences on intestinal homeostasis, does not constitute a facilitating factor to colitis in predisposed individuals nor to gastrointestinal infections in wild type mice. [ABSTRACT FROM AUTHOR]

Dominant females of cooperative breeding species often use aggression to suppress reproduction of subordinate females, resulting in subordinates experiencing stress-related increases in glucocorticoid levels, which may cause reproductive down-regulation. This would suggest a general pattern with higher glucocorticoid levels in subordinate compared to dominant individuals; however, the opposite was found in a number of cooperatively breeding species. Furthermore, breeding females of the cooperatively breeding Damaraland mole-rats ( Fukomys damarensis ) exhibit very high androgen concentrations during the wet season, presumably to support their breeding monopoly. Hormone analysis in Damaraland mole-rats have typically been measured using plasma and urine, but faecal analysis offers additional advantages especially for field studies on this species. The present study examines the suitability of Damaraland mole-rat faecal samples for determining glucocorticoid metabolite (fGCM) and androgen metabolite (fAM) concentrations using enzyme immunoassays. Using these assays, we further evaluated the effects of breeding status on fGCM and fAM concentrations in wild-caught and captive Damaraland mole-rats. Wild-caught breeding and non-breeding males and females exhibited no differences in fAM concentrations. Immunoreactive fGCM concentrations were only high in male breeders and comparatively low in non-breeders and breeding females. Concentrations of fAMs and fGCMs were similar in captive males and females, but fAM concentrations were elevated in captive compared to wild-caught individuals, which may be related to a higher reproductive activity due to removal from the breeding female. The relatively uniform fAM and fGCM concentrations found in wild-caught mole-rats may be explained by a stable colony structure during the dry season during which this study was conducted. Limited dispersal opportunities result in lower aggression and stress levels within a colony and as a result lower fAM and fGCM concentrations. [ABSTRACT FROM AUTHOR]

Several hormones are potential indicators of stress in free-ranging animals and provide information on animal health in managed-care settings. In response to stress, glucocorticoids (GC, e.g. cortisol) first appear in circulation but are later incorporated into other tissues (e.g. adipose) or excreted in feces or urine. These alternative matrices can be sampled remotely, or by less invasive means, than required for blood collection and are especially valuable in highly mobile species, like marine mammals. We characterized the timing and magnitude of several hormones in response to a stressor in bottlenose dolphins ( Tursiops truncatus ) and the subsequent incorporation of cortisol into blubber, and its metabolites excreted in feces. We evaluated the endocrine response to an acute stressor in bottlenose dolphins under managed care. We used a standardized stress protocol where dolphins voluntarily beached onto a padded platform and remained out of water for two hours; during the stress test blood samples were collected every 15 min and blubber biopsies were collected every hour (0, 60, and 120 min). Each subject was studied over five days: voluntary blood samples were collected on each of two days prior to the stress test; 1 and 2 h after the conclusion of the out-of-water stress test; and on the following two days after the stress test. Fecal samples were collected daily, each afternoon. The acute stressor resulted in increases in circulating ACTH, cortisol, and aldosterone during the stress test, and each returned to baseline levels within 2 h of the dolphin’s return to water. Both cortisol and aldosterone concentrations were correlated with ACTH, suggesting both corticosteroids are at least partly regulated by ACTH. Thyroid hormone concentrations were generally unaffected by the acute stressor. Blubber cortisol increased during the stress test, and fecal GC excretion was elevated on the day of the stress test. We found that GCs in bottlenose dolphins can recover within hours of acute stress, and that cortisol release can be detected in alternate matrices within a few hours—within 2 h in blubber, and 3.5–5 h in fecal samples. [ABSTRACT FROM AUTHOR]

Abstract: Background: The advent of non‐invasive methods provides a powerful alternative to stress studies as the use of stressful handling techniques is no longer needed. However, many factors influence hormone metabolism such as sex, diet, and metabolic rate. Thus, validation should be species‐ and matrix‐specific. Methods: To assess stress response in brown howler monkeys Alouatta clamitans, we adopted an ACTH challenge test and parallelism to provide physiological and laboratorial validation. Radioimmunoassay was used to measure fecal levels of corticosterone. Results and Conclusions: All challenged animals presented a peak in fecal glucocorticoids levels the day after the treatment, while control animals did not. There were no significant sex differences, but females with infants had higher levels of corticosterone. Corticosterone levels showed parallelism to the standard curve of the diagnostics kit. Collectively, the data suggest that the method was validated and is useful for monitoring stress, thereby helping in conservation programs both in captivity and in the wild. Transit time information may be coupled with travel distance in seed dispersal studies. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction, social communication, and repetitive and stereotyped behaviors. Recent work has begun to explore gene × environmental interactions in the etiology of ASD. We previously reported that prenatal stress exposure in stress-susceptible heterozygous serotonin transporter (SERT) KO pregnant dams in a mouse model resulted in autism-like behavior in the offspring (SERT/S mice). The association between prenatal stress and ASD appears to be affected by maternal SERT genotype in clinical populations as well. Using the mouse model, we examined autistic-like behaviors in greater detail, and additionally explored whether diet supplementation with docosahexaenoic acid (DHA) may mitigate the behavioral changes. Only male SERT/S mice showed social impairment and stereotyped behavior, and DHA supplementation ameliorated some of these behaviors. We also measured monoamine levels in the SERT/S mice after three treatment paradigms: DHA-rich diet continuously from breeding (DHA diet), DHA-rich diet only after weaning (CTL/DHA diet) and control diet only (CTL diet). The dopamine (DA) content in the striatum was significantly increased in the SERT/S mice compared with wild-type (WT) mice, whereas no difference was observed with noradrenaline and serotonin content. Moreover, DA content in the striatum was significantly reduced in the SERT/S mice with the DHA-rich diet provided continuously from breeding. The results indicate that autism-associated behaviors and changes in the dopaminergic system in this setting can be mitigated with DHA supplementation. [ABSTRACT FROM AUTHOR]

In young (3-month-old) male Wistar rats, we studied the effects of intrahippocampal microinjections of melipramin under conditions of emotional stress induced by sessions of electrical nociceptive stimulation of the limbs. In most cases, seven-day-long stressing resulted in suppression of electrical activity of the hippocampus, exerted ambivalent effects on the frequency of brain self-stimulation (BSS) events, decreased the communicability of animals in the two-chamber test, and increased the latencies of going of the animal from the arena center and grooming episodes in the open field test. Injections of melipramin interfered with the development of stress-induced disorders in the hippocampus, decreased the normalized content of beta oscillations in the neocortex and the theta-index in the hypothalamus, increased the BSS frequency, and decreased the level of negativation of the behavioral manifestations of this phenomenon. The duration of stay of a rat near the partition in the two-chamber test increased, the mobility and number of grooming episodes in the open field enhanced, but the latency of leaving the arena center also increased (similarly to what was observed in the control). On the 8th-9th day of the poststress period, behavioral disorders of rats of the control group in the two-chamber test were smoothed to a significant extent. The stability of the examined indices or the reverse development of stress-induced disorders within the above period in animals injected with melipramin were indicative of a significant role of the hippocampus in the formation of central effects of this antidepressant and also of adaptogenic and stress-protective properties of this drug. [ABSTRACT FROM AUTHOR]

Variations in the early postnatal environment of rodents produce long-term changes in responses to stress that may underlie neuropsychiatric diseases such as anxiety, depression and schizophrenia. GABA A receptors undergo marked changes in their subunit composition during this period, involving a regionally-dependent replacement of α 2 with α 1 subunits, the so-called α-subunit switch. In this study we examined the effects of early-life environment on adulthood GABA A receptor α 1 and α 2 subunit expression and the synaptic clustering of GABA A receptors. Male and female mice were exposed to either 15 min daily handling sessions (EH) or no intervention (NH) over postnatal day (PND) 1–14. Adulthood behavioural differences in anxiety were assessed on the elevated plus-maze. Immunoperoxidase histochemistry was used to examine the density of the α 1 and α 2 subunit proteins. Double-labelling immunofluorescence and confocal microscopy were used to study GABA A receptor synaptic clustering. NH animals showed increased anxiety-type behaviours in the elevated plus maze relative to EH mice. NH males showed a loss of α 2 subunits from the thalamus and lower layers of the somatosensory cortex, whilst NH females showed a reduction of α 2 but increase in α 1 protein in lower layers of the primary somatosensory cortex only. The NH condition also reduced α 1 subunit expression in dentate gyrus (DG) in both males and females. Regardless of sex, NH mice showed reduced colocalisation of GABA A receptor α 2 subunits with the synaptic marker gephyrin relative to the control condition. These findings suggest that early-life environment has long-lasting effects on GABA A receptors, leading to long-term changes in adulthood behaviour, and are of relevance to neurodevelopmental explanations of stress-augmented neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Aim: To investigate the behavioral deficits, cognitive impairment and possible mechanisms induced by chronic unpredictable stress (CUS) in mice of different ages. Methods: The behaviors and cognition were tested using the open field test, tail suspension test and the Morris water maze. The changes in the insulin-like growth factor II (IGF-II) and the extracellular signal-regulated kinase (ERK) and phosphorylation (p-ERK) in the hippocampus (HP) and prefrontal cortex (PFC) were evaluated by immunohistochemistry. Results: The 15-month-old mice revealed a significant decline in spontaneous behavior and the learning–memory function and showed a decrease in IGF-II and p-ERK expression levels in HP and PFC. Four weeks of CUS exposure induced significant anxiety- and depression-like behavior and learning–memory function impairment in 3- to 15-month-old mice, and reduced IGF-II and p-ERK expression levels in HP and PFC, compared with control group mice, respectively. Conclusions: The behavioral deficits and cognitive impairment induced by CUS and aging in mice could be associated with the down-regulated expression of IGF-II and p-ERK in HP and PFC. This role seems to be dependent on the intracellular ERK pathway. [ABSTRACT FROM AUTHOR]

Evidence indicates that release of pro-inflammatory cytokines induced by social stress contributes to affective disorders. Additionally, there are known sex differences in both the stress response and the stressors that can elicit this response. In this regard, the chronic social instability (CSI) rodent model of stress appears to be the best fit for the social nature of females. This study analyzed the effects of CSI on female mouse behavior, hippocampal cytokine expression, tryptophan metabolism and monoaminergic activity. The activity of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes were also measured. Results showed a decrease in sucrose consumption in stressed subjects, indicative of anhedonic behavior and an increase in climbing activity in the forced swimming test (FST) and in whisking behavior, which have been associated with anxiety. Decreased interleukin-10 (IL-10) expression was found in the hippocampus of the stressed mice, while no differences in pro-inflammatory cytokine expression and tryptophan (TRYP), kynurenine (KYN) or 3-hydroxy kynurenine (3-HK) levels were found. Increased hippocampal serotoninergic and noradrenergic activity was observed in stressed mice. The higher plasma corticosterone and lower hypothalamic glucocorticoid receptor (GR) expression levels showed an increase in HPA activity after CSI. No differences were found in the plasma estradiol levels or the central estrogen receptors (ERα and ERβ) expression levels. These data indicate that the CSI stress-induced behavioral and physiological changes associated with anxiety and depressive disorders. Although additional studies are warranted, the results suggest an involvement of anti-inflammatory cytokines in the biobehavioral effects of social stress in female mice. [ABSTRACT FROM AUTHOR]

The negative emotional consequences associated with life stress exposure in an individual can affect the emotional state of social partners. In this study, we describe an experimental rat model of social stress contagion and its effects on social behaviour and cardiac autonomic and neuroendocrine functions. Adult male Wistar rats were pair-housed and one animal (designated as “demonstrator” (DEM)) was submitted to either social defeat stress (STR) by an aggressive male Wild-type rat in a separate room or just exposed to an unfamiliar empty cage (control condition, CTR), once a day for 4 consecutive days. We evaluated the influence of cohabitation with a STR DEM on behavioural, cardiac autonomic and neuroendocrine outcomes in the cagemate (defined “observer” (OBS)). After repeated social stress, STR DEM rats showed clear signs of social avoidance when tested in a new social context compared to CTR DEM rats. Interestingly, also their cagemate STR OBSs showed higher levels of social avoidance compared to CTR OBSs. Moreover, STR OBS rats exhibited a higher heart rate and a larger shift of cardiac autonomic balance toward sympathetic prevalence (as indexed by heart rate variability analysis) immediately after the first reunification with their STR DEMs, compared to the control condition. This heightened cardiac autonomic responsiveness habituated over time. Finally, STR OBSs showed elevated plasma corticosterone levels at the end of the experimental protocol compared to CTR OBSs. These findings demonstrate that cohabitation with a DEM rat, which has experienced repeated social defeat stress, substantially disrupts social behaviour and induces short-lasting cardiac autonomic activation and hypothalamic-pituitary-adrenal axis hyperactivity in the OBS rat, thus suggesting emotional state-matching between the OBS and the DEM rats. We conclude that this rodent model may be further exploited for investigating the neurobiological bases of negative affective sharing between social partners under chronic social stress conditions. [ABSTRACT FROM AUTHOR]

Although millions of cats live among humans worldwide the scientific community knows relatively little about cat behavior and cognition. Olfaction is an important perceptual sense for many members of Carnivora, however the role of chemical signals in cat social relationships is not fully understood. Research indicates chemical signals play an important role in many areas of cat behavior including mother-offspring and conspecific interactions and exploration of their environment. Chemical cues appear to play a role in stress and anxiety reduction, allowing cats to feel secure in their environment. A better understanding of cat chemical signals, especially as it relates to within and between species communication, may lead to an increase in cat wellbeing as humans can utilize this knowledge in applied settings. Therefore, the purpose of this review is to investigate how cats process and use chemical signals in social contexts and identify ways this information can be applied to address cat behavioral issues, such as inappropriate litter box and scratching behavior, and improve cat welfare, including species-appropriate ways of reinforcing the human-cat bond. [ABSTRACT FROM AUTHOR]

Several reports indicate that psychological stress and depression are detrimental to health and that chronic stress implicates pathophysiology of mood and anxiety- related disorders, thus leading to several stress-related complications. The present study focuses on behavioural status and neurochemical variations in myelin of rat brain exposed to chronic immobilization stress and evaluates the effect of fruit juice of noni over changes in the myelin content of forebrain (FB) and midbrain (MB) regions of rats exposed to stress. Immobilization stress (IS) strategy was utilized to induce stress in Wistar rats. Myelin protein was isolated from the MB and FB regions of rats. Assessment of activities of membrane bound enzymes, levels of neurotransmitters (dopamine, serotonin and glutamate of FB and MB) and lipid profile of myelin in addition to behavioural analysis were carried out. The membrane- bound enzymes such as ATPases, 5'-nucleotidase and acetylcholinesterase exhibit significant decrease in their activities both in the FB and MB regions on stress induction, when compared to that of control. The neurotransmitters and lipid profile also show similar pattern among the experimental group. However, administration of noni juice (NJ) in IS exposed rats can significantly alter the activities of myelin-associated enzymes and levels of neurotransmitters and lipid content of myelin (P < 0.05) along with improvement in the behavioural pattern when compared to those of IS rats. These preliminary results set targets for further authentication of the use of NJ against stress. This NJ could become one of the ideal supplements for management of stress-induced neurological disorders. [ABSTRACT FROM AUTHOR]

Our group has recently provided novel insights into a poorly understood component of intercommunication between the brain and the immune system by showing that psychological stress can modify lymphocytes in a manner that may boost resilience to psychological stress. To demonstrate the influence of the adaptive immune system on mood states, we previously showed that cells from lymph nodes of socially defeated mice, but not from unstressed mice, conferred anxiolytic and antidepressant-like effects and elevated hippocampal cell proliferation when transferred into naïve lymphopenic Rag2 −/− mice. In the present study, we asked whether similar transfer could be anxiolytic and antidepressant when done in animals that had been rendered anxious and depressed by chronic psychological stress. First, we demonstrated that lymphopenic Rag2 −/− mice and their wild-type C57BL/6 mouse counterparts had similar levels of affect normally. Second, we found that following chronic (14 days) restraint stress, both groups displayed an anxious and depressive-like phenotype and decreased hippocampal cell proliferation. Third, we showed that behavior in the open field test and light/dark box was normalized in the restraint-stressed Rag2 −/− mice following adoptive transfer of lymph node cells from green fluorescent protein (GFP) expressing donor mice previously exposed to chronic (14 days) of social defeat stress. Cells transferred from unstressed donor mice had no effect on behavior. Immunolabeling of GFP+ cells confirmed that tissue engraftment had occurred at 14 days after transfer. We found GFP+ lymphocytes in the spleen, lymph nodes, blood, choroid plexus, and meninges of the recipient Rag2 −/− mice. The findings suggest that the adaptive immune system may play a key role in promoting recovery from chronic stress. The data support using lymphocytes as a novel therapeutic target for anxiety states. [ABSTRACT FROM AUTHOR]

Stress is a contributing factor to the development and maintenance of addiction in humans. However, few studies have shown that stress potentiates the rewarding and/or reinforcing effects of methamphetamine in rodent models of addiction. The present study assessed the effects of exposure to 14 days of chronic variable stress (CVS), or no stress as a control (CON), on the rewarding and reinforcing effects of methamphetamine in adult rats using the conditioned place preference (Experiment 1) and intravenous self-administration (Experiment 2) paradigms. In Experiment 2, we also assessed individual differences in open field locomotor activity, anxiety-like behavior in the elevated plus maze (EPM), and physiological responses to a novel environment as possible predictors of methamphetamine intake patterns. Exposure to CVS for 14 days did not affect overall measures of methamphetamine conditioned reward or reinforcement. However, analyses of individual differences and direct vs. indirect effects revealed that rats exhibiting high physiological reactivity and locomotor activity in the EPM and open field tests self-administered more methamphetamine and reached higher breakpoints for drug reinforcement than rats exhibiting low reactivity. In addition, CVS exposure significantly increased the proportion of rats that exhibited high reactivity, and high reactivity was significantly correlated with increased levels of methamphetamine intake. These findings suggest that individual differences in physiological and locomotor reactivity to novel environments, as well as their interactions with stress history, predict patterns of drug intake in rodent models of methamphetamine addiction. Such predictors may eventually inform future strategies for implementing individualized treatment strategies for amphetamine use disorders. [ABSTRACT FROM AUTHOR]

Background: Chronic stress is associated with increased risk of glucose intolerance and cardiovascular diseases, albeit through undefined mechanisms. With the aim of gaining insights into the latter, this study examined the metabolic profile of young adult male rats that were exposed to chronic unpredictable stress. Methods: Young adult male rats were submitted to 4 weeks of chronic unpredictable stress and allowed to recover for 5 weeks. An extensive analysis including of morphologic, biochemical and molecular parameters was carried out both after chronic unpredictable stress and after recovery from stress. Results: After 28 days of chronic unpredictable stress (CUS) the animals submitted to this protocol displayed less weight gain than control animals. After 5 weeks of recovery the weight gain rebounded to similar values of controls. In addition, following CUS, fasting insulin levels were increased and were accompanied by signs of impaired glucose tolerance and elevated serum corticosteroid levels. This biochemical profile persisted into the post-stress recovery period, despite the restoration of baseline corticosteroid levels. The mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)-γ and lipocalin-2 in white adipose tissue were, respectively, down- and up-regulated. Conclusions: Reduction of PPAR-γ expression and generation of a pro-inflammatory environment by increased lipocalin-2 expression in white adipose tissue may contribute to stress-induced glucose intolerance. [ABSTRACT FROM AUTHOR]

Background: In recent decades there has been a growing concern about animal stress on intensive pig farms due to the undesirable consequences that stress produces in the normal physiology of pigs and its effects on their welfare and general productive performance. This review analyses the most important types of stress (social, environmental, metabolic, immunological and due to human handling), and their biological consequences for pigs. The physio-pathological changes associated with stress are described, as well as the negative effects of stress on pig production. In addition an update of the different biomarkers used for the evaluation of stress is provided. These biomarkers can be classified into four groups according to the physiological system or axis evaluated: sympathetic nervous system, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and immune system. Conclusions: Stress it is a process with multifactorial causes and produces an organic response that generates negative effects on animal health and production. Ideally, a panel of various biomarkers should be used to assess and evaluate the stress resulting from diverse causes and the different physiological systems involved in the stress response. We hope that this review will increase the understanding of the stress process, contribute to a better control and reduction of potential stressful stimuli in pigs and, finally, encourage future studies and developments to better monitor, detect and manage stress on pig farms. [ABSTRACT FROM AUTHOR]

Catecholamines (CAs) are mainly produced by sympathoadrenal system but theirde novoproduction has been also observed in adipose tissue cells. The aim of this work was to investigate whether immune challenge induced by lipopolysaccharide (LPS) modulates biosynthesis of CAs in mesenteric adipose tissue (MWAT), as well as whether previous exposure to immobilization (IMO) stress could modulate this process. Sprague–Dawley rats were exposed to single (2 h) or repeated (2 h/7 days) IMO and afterwards injected with LPS (i.p., 100 μg/kg body weight) and sacrificed 3 h later. LPS did not alter CA biosynthesis in MWAT in control rats. Single and repeated IMO elevated CAs and expression of CA biosynthetic enzymes in MWAT, including adipocyte and stromal/vascular fractions (SVF). Repeated IMO followed by LPS treatment led to the up-regulation of CA-biosynthetic enzymes expression, elevation of CAs in SVF but depletion of norepinephrine and epinephrine in adipocyte fraction. Prior IMO caused a marked LPS-induced macrophage infiltration in MWAT as evaluated by F4/80 expression. A positive correlation between expression of tyrosine hydroxylase and F4/80 suggests macrophages as the main source of LPS-induced CA production in MWAT. Furthermore, prior exposure to the single or repeated IMO differently affected immune responses following LPS treatment by modulation of inflammatory cytokine expression. These data suggest that stress might be a significant modulator of immune response in MWAT via stimulation of the macrophage infiltration associated with cytokine response andde novoproduction of CAs. [ABSTRACT FROM PUBLISHER]

Neurobiological mechanisms underlying comorbid posttraumatic stress disorder (PTSD) and cocaine use disorder (CUD) are unknown. We aimed to develop an animal model of PTSD + CUD to examine the neurobiology underlying cocaine-seeking in the presence of PTSD comorbidity. Rats were exposed to cat urine once for 10-minutes and tested for anxiety-like behaviors one week later. Subsequently, rats underwent long-access (LgA) cocaine self-administration and extinction training. Rats were re-exposed to the trauma context and then immediately tested for cue-primed reinstatement of cocaine-seeking. Plasma and brains were collected afterwards for corticosterone assays and real-time qPCR analysis. Urine-exposed (UE;n = 23) and controls not exposed to urine (Ctrl;n = 11) did not differ in elevated plus maze behavior, but UE rats displayed significantly reduced habituation of the acoustic startle response (ASR) relative to Ctrl rats. A median split of ASR habituation scores was used to classify stress-responsive rats. UE rats (n = 10) self-administered more cocaine on Day 1 of LgA than control rats (Ctrl + Coc;n = 8). Re-exposure to the trauma context prevented cocaine reinstatement only in stress-responsive rats. Ctrl + Coc rats had lower plasma corticosterone concentrations than Ctrls, and decreased gene expression of corticotropin releasing hormone (CRH) and Glcci1 in the hippocampus. Rats that self-administered cocaine displayed greater CRH expression in the amygdala that was independent of urine exposure. While we did not find that cat urine exposure induced a PTSD-like phenotype in our rats, the present study underscores the need to separate stressed rats into cohorts based on anxiety-like behavior in order to study individual vulnerability to PTSD + CUD. [ABSTRACT FROM PUBLISHER]

The stress experienced by an animal is ameliorated when the animal is exposed to distressing stimuli along with a conspecific animal(s). This is known as social buffering. Previously, we found that the presence of an unfamiliar male rat induced social buffering and ameliorated conditioned fear responses of a male rat subjected to an auditory conditioned stimulus (CS). However, because our knowledge of social buffering is highly biased towards findings in male subjects, analyses using female subjects are crucial for comprehensively understanding the social buffering phenomenon. In the present studies, we assessed social buffering of conditioned fear responses in female rats. We found that the estrus cycle did not affect the intensity of the rats' fear responses to the CS or their degree of vigilance due to the presence of a conspecific animal. Based on these findings, we then assessed whether social buffering ameliorated conditioned fear responses in female rats without taking into account their estrus cycles. When fear conditioned female rats were exposed to the CS without the presence of a conspecific, they exhibited behavioral responses, including freezing, and elevated corticosterone levels. By contrast, the presence of an unfamiliar female rat suppressed these responses. Based on these findings, we conclude that social buffering can ameliorate conditioned fear responses in female rats. [ABSTRACT FROM AUTHOR]

The relationship between stress response and positive affective states is thought to be bidirectional: whilst stress can lead to a blunted hedonic response, positive affect reduces the negative effects of stress. We have previously shown that persistently high positive affectivity as measured by 50-kHz ultrasonic vocalizations (USVs) is protective against chronic variable stress (CVS). The present study examined the effect of CVS on 50-kHz USVs elicited by amphetamine administration, simultaneously considering the stable inter-individual differences in positive affectivity. Forty juvenile male Wistar rats were categorised as of high (HC) or low (LC) positive affectivity based on their 50-kHz USV response to imitation of rough-and-tumble play (‘tickling’). As adults, the rats were subjected to four weeks of CVS, after which D -amphetamine was administered in five daily doses followed by a challenge dose (all 1 mg/kg IP) nine days later. CVS reduced sucrose preference in LC-rats only. After CVS, amphetamine-elicited 50-kHz USVs were significantly reduced in LC-rats, the effect of stress in HC-rats being smaller and less consistent. In previously stressed and amphetamine-treated LC-rats, locomotor response to amphetamine was attenuated. In stressed LC-rats, DOPAC levels and dopamine turnover were increased in striatum after amphetamine treatment, and dopamine D 1 receptor levels were upregulated in nucleus accumbens. LC-rats had lower isoleucine levels in frontal cortex. These results show that stress-related changes in response to amphetamine are dependent on inter-individual differences in positive affectivity both at neurochemical and behavioural levels, and further support the notion of higher vulnerability of animals with low positive affect. [ABSTRACT FROM AUTHOR]

Due to their direct inaccessibility, affective states are classically assessed by gathering concomitant physiological and behavioral measures. Although such a dual approach to assess emotional states is frequently used in different species including humans, the invasiveness of procedures for physiological recordings particularly in smaller-sized animals strongly restricts their application. We used infrared thermography, a non-invasive method, to assess physiological arousal during open field and elevated plus maze tests in mice. By measuring changes in surface temperature indicative of the animals' emotional response, we aimed to improve the inherently limited and still controversial information provided by behavioral parameters commonly used in these tests. Our results showed significant and consistent thermal responses during both tests, in accordance with classical physiological responses occurring in stressful situations. Besides, we found correlations between these thermal responses and the occurrence of anxiety-related behaviors. Furthermore, initial temperatures measured at the start of each procedure (open field, elevated plus maze), which can be interpreted as a measure of the animals' initial physiological arousal, predicted the levels of activity and of anxiety-related behaviors displayed during the tests. Our results stress the strong link between physiological correlates of emotions and behaviors expressed during unconditioned fear tests. [ABSTRACT FROM AUTHOR]

The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 min of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-h intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-min to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similar attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress. [ABSTRACT FROM AUTHOR]

Psychological stress increases intestinal permeability, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders. We assessed the effect of subacute, chronic and combined stress on intestinal barrier function and mast cell density. Male Wistar rats were allocated to four experimental groups (n = 8/group): 1/sham; 2/subacute stress (isolation and limited movement for 24 h); 3/chronic crowding stress for 14 days and 4/combined subacute and chronic stress. Jejunum and colon were collected to measure: transepithelial electrical resistance (TEER; a measure of epithelial barrier function); gene expression of tight junction molecules; mast cell density. Plasma corticosterone concentration was increased in all three stress conditions versus sham, with highest concentrations in the combined stress condition. TEER in the jejunum was decreased in all stress conditions, but was significantly lower in the combined stress condition than in the other groups. TEER in the jejunum correlated negatively with corticosterone concentration. Increased expression of claudin 1, 5 and 8, occludin and zonula occludens 1 mRNAs was detected after subacute stress in the jejunum. In contrast, colonic TEER was decreased only after combined stress, and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the chronic and combined stress condition in the colon only. In conclusion, our data show that chronic stress sensitizes the gastrointestinal tract to the effects of subacute stress on intestinal barrier function; different underlying cellular and molecular alterations are indicated in the small intestine versus the colon. [ABSTRACT FROM PUBLISHER]

Stress in pregnant rats caused by chronic immobilization alters the pattern of secretion of corticosterone and modifies the hypothalamic-pituitary-adrenal axis (HPA) of the fetus. Early postnatal handling, however, may reverse the effects of increased secretion of corticosterone. We investigated the effects of prenatal stress and postnatal handling on the activity of the HPA axis of male offspring of stressed female rats. Male 90-day-old rats from four groups were investigated: prenatally stressed animals without postnatal handling, prenatally stressed animals with postnatal handling, unstressed control animals with postnatal handling, and unstressed control animals without postnatal handling. After sacrifice, the adrenal glands were weighed to determine the adrenal-somatic index. Apoptosis was evaluated by TUNEL assay and active caspase-3 expression. We found that the adrenal gland cortex:medulla ratio increased in animals with prenatal stress and that eventually the stress caused apoptosis. Handling newborns to simulate maternal activity ameliorated some of the negative effects of prenatal stress. [ABSTRACT FROM AUTHOR]

Several organisms irrespective of their complexity in structure and function have an inbuilt circadian rhythm. Zebrafish could be used as an alternate model animal in sleep research as it exhibits similar sleep-wake dynamics as mammals and Drosophila. In this study, we have analysed the adult zebrafish brain for its differential proteome and gene expression during perturbed light/dark cycle. A total of 53 and 25 proteins including sncb, peroxiredoxins and TCR alpha were identified based on two-dimensional gel electrophoresis Fourier transform mass spectrometer/ion trap tandem mass spectrometer and differential in-gel electrophoresis MALDI TOF MS/ MS analysis, respectively, with at least 1.5-fold changes between the control and experimental brains. Real time-polymerase chain reaction revealed that many circadian pathway-associated genes, such as per1b, bmal1b, cry1b, bmal2 and nr1d2, were differentially regulated during continuous light/dark exposures. It is hypothesized that the differential regulation of these genes might lead to the discovery of potential diagnostic markers for gaining insight into the light/dark-associated stress in humans. [ABSTRACT FROM AUTHOR]

Brucella melitensis is a facultative intracellular pathogen. The regM gene encodes a sensory transduction protein kinase in B. melitensis 16M, and genes orthologous to regM have been found to exist in many bacterial species. However, little is known about the regulation function of this gene in Brucella. In order to characterize this gene, we constructed a marked deletion mutant of regM as well as its complemented strain. The mutant was less able to withstand acid and hyperosmotic conditions than wild-type strain but shown no significant difference with wild-type strain when challenged by elevated temperature and hypotonic conditions. In addition, inactivation of regM did not affect virulence in B. melitensis 16M in macrophage and mice infection models. [ABSTRACT FROM AUTHOR]

Neuropeptide substance P (SP) and reactive oxygen species (ROS) have been demonstrated to play an important role in psychological stress-induced alteration of hair cycle, the underlying mechanism remains unknown. The present study aims to investigate possible contribution of SP and ROS in chronic restraint stress (CRS, a chronic psychological stress model) induced abnormal of hair cycle and induction of autophagy. Mouse CRS model was applied for 18 days with or without treatment antioxidant Tempol (a free radical scavenger) or SP receptor (NK1) antagonist (RP67580). After CRS procedure, hair growth cycle, oxidative stress markers and skin tissue autophagy levels were analyzed by ELISA or western blot. Our results revealed that CRS reduced body weight gain, distance of movement and times of standing, affected hair cycle by prolonging the telogen stage and delaying subsequent anagen and catagen stage. In addition, CRS resulted in increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase of autophagy markers (microtubule-associated proteins, light chain 3-II, LC3-II, and Beclin-1) in mice skin. Treatment with Tempol restored GSH-Px activity, and significantly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, as well as normalized hair cycle. In addition; RP67580 also restored SOD and GSH-Px activities, and markedly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, and normalized hair cycle. Our study provides the first strong evidence for SP and ROS play a role not only in alteration of hair cycle but also in induction of autophagy in psychological stress model, suggesting autophagy may contribute to psychological stress-induced abnormal of hair cycle. [ABSTRACT FROM AUTHOR]

We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2-/- mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice. The mice receiving lymphocytes from defeated donors showed less anxiety, more social behavior, and increased hippocampal cell proliferation compared with those receiving no cells or cells from unstressed donors. Mice receiving stressed immune cells had reduced pro-inflammatory cytokine levels in the blood relative to the other groups, an effect opposite to the elevated donor pro-inflammatory cytokine profile. Furthermore, mice receiving stressed immune cells had microglia skewed toward an anti-inflammatory, neuroprotective M2-like phenotype, an effect opposite the stressed donors' M1-like pro-inflammatory profile. However, stress had no effect on lymphocyte surface marker profiles in both donor and recipient mice. The data suggest that chronic stress-induced changes in the adaptive immune system, contrary to conferring anxiety and depressive behavior, protect against the deleterious effects of stress. Improvement in affective behavior is potentially mediated by reduced peripheral pro-inflammatory cytokine load, protective microglial activity, and increased hippocampal cell proliferation. The data identify the peripheral adaptive immune system as putatively involved in the mechanisms underlying stress resilience and a potential basis for developing novel rapid-acting antidepressant therapies. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) nowsitswithin the newly created "Trauma- and Stressor-Related Disorders" section of the Diagnostic and Statistical Manual of Mental Disorders (fifth edition; DSM-5). Through the refinement and expansion of diagnostic criteria, the DSM-5 version better clarifies the broad and pervasive effects of trauma on functioning, as well as the impact of development on trauma reactions. Aggressive and dissociative symptoms are more thoroughly characterized, reflecting increasing evidence that reactions to trauma often reach beyond the domains of fear and anxiety (these latter domains were emphasized in DSM-IV). These revised criteria are supported by decades of preclinical and clinical research quantifying traumatic stress-induced changes in neurobiological and behavioral function. Several features of the DSM-5 PTSD criteria are similarly and consistently represented in preclinical animal models and humans following exposure to extreme stress. In rodent models, for example, increases in anxiety-like, helplessness, or aggressive behavior, along with disruptions in circadian/neurovegetative function, are typically induced by severe, inescapable, and uncontrollable stress. These abnormalities are prominent features of PTSD and can help us in understanding the pathophysiology of this and other stress-associated psychiatric disorders. In this article we examine some of the changes to the diagnostic criteria of PTSD in the context of trauma-related neurobiological dysfunction, and discuss implications for how preclinical data can be useful in current and future clinical conceptualizations of trauma and traumarelated psychiatric disorders. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS)-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS) and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2% in drinking water) decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and SI tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY), a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis. [ABSTRACT FROM AUTHOR]

Several behavioral interventions, based on social enrichment and observational learning are applied in treatment of neuropsychiatric disorders. However, the mechanism of such modulatory effect and the safety of applied methods on individuals involved in social support need further investigation. We took advantage of known differences between inbred mouse strains to reveal the effect of social enrichment on behavior and neurobiology of animals with different behavioral phenotypes. C57BL/6 and DBA/2 female mice displaying multiple differences in cognitive, social, and emotional behavior were group-housed either in same-strain or in mixed-strain conditions. Comprehensive behavioral phenotyping and analysis of expression of several plasticity- and stress-related genes were done to measure the reciprocal effects of social interaction between the strains. Contrary to our expectation, mixed housing did not change the behavior of DBA/2 mice. Nevertheless, the level of serum corticosterone and the expression of glucocorticoid receptor Nr3c1 in the brain were increased in mixed housed DBA/2 as compared with those of separately housed DBA/2 mice. In contrast, socially active C57BL/6 animals were more sensitive to the mixed housing, displaying several signs of stress: alterations in learning, social, and anxiety-like behavior and anhedonia. These behavioral impairments were accompanied by the elevated serum corticosterone and the reduced expression of Nr3c1, as well as the elevated Bdnf levels in the cortex and hippocampus. Our results demonstrate the importance of social factors in modulation of both behavior and the underlying neurobiological mechanisms in stress response, and draw attention to the potential negative impact of social interventions for individuals involved in social support. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the effects of probiotic therapy (PT) in rats with ligature-induced periodontitis associated with restraint stress. Methods: Sixty-four rats were divided into control, stress (STR), probiotic (PROB), periodontal disease (PD), STRPROB, STR-PD, STR-PROB-PD, and PROB-PD groups. The probiotic was added to the drinking water for 44 days. PD was induced by a ligature. In STR groups, the animals were subjected to restraint stress for 2.5 hours per day for 30 days. Results: Rats with PD exhibited increased alveolar bone loss (P <0.05), as well as increased levels of cyclooxygenase-2, serum C-terminal telopeptide (CTX), p38 mitogen-activated protein kinase (p38), and receptor activator of nuclear factor-xB ligand and decreased levels of osteoprotegerin (OPG). Stressed rats presented high levels of C-peptide, corticosterone, and glucose (P <0.05). In general, the presence of stress reduced the expression of CTX and p38 (P <0.05). PT reduced alveolar bone loss in unstressed animals. It also decreased expression of CTX and induced increased expression of OPG in unstressed animals with PD. However, PT was not effective in preventing bone loss or altering the expression of inflammatory markers in stressed animals. PT decreased the number of inflammatory cells in the periodontal tissue (P <0.05). Groups with stress and PD showed decreased villous height and crypt depth. Stress seemed to prevent part of the probiotic beneficial effects on the small intestine. Conclusions: Based on the methodology used, PT may reduce tissue breakdown resulting from PD in unstressed rats. The protocol used for restraint stress influenced the immunomodulatory effects of PT in intestinal and periodontal tissues. [ABSTRACT FROM AUTHOR]

In modern intensive husbandry, systems often restrict farm animal behavior. Behavioral needs will be generated by external stimuli such as stressors deriving from environmental factors or the method of animal care, or some internal factor in farm animals. This means that behavioral restriction would induce maladaptation to stressors or chronic stress. Such a risk of behavioral restriction degrades an animal's physical and mental health and leads to economic loss at a farm. Methods to reduce the risk of behavioral restrictions are to ameliorate the source of a stressor through adequate animal management or to carry out environmental enrichment. This review is intended to describe the relation between animal management and behavioral needs from the perspective of animal motivation. [ABSTRACT FROM AUTHOR]

We studied the effect of terahertz waves (NO frequency range, 150.176-150.664 GHz) on stress-induced variations in behavioral reactions of male albino rats during hypokinetic stress. THz irradiation was followed by partial or complete normalization of behavioral reactions of male albino rats after hypokinetic stress. The most signifi cant effect was observed after continuous irradiation for 30 min. [ABSTRACT FROM AUTHOR]

Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9mA each) delivered before memory testing reversed the memory retrieval pattern (MRP) in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non-stress condition) to mPFC-dependent MRP and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay. [ABSTRACT FROM AUTHOR]

Rationale: Adverse social experience in adolescence causes reduced medial prefrontal cortex (mPFC) dopamine (DA) and associated behavioral deficits in early adulthood. Objective: This study aims to determine whether mPFC DA hypofunction following social stress is specific to adolescent experience and if this results from stress-induced DA D receptor activation. Materials and methods: Male rats exposed to repeated social defeat during adolescence or adulthood had mPFC DA activity sampled 17 days later. Separate experiments used freely moving microdialysis to measure mPFC DA release in response to adolescent defeat exposure. At P40, 49 and 56 mPFC DA turnover was assessed to identify when DA activity decreased in relation to the adolescent defeat experience. Finally, nondefeated adolescent rats received repeated intra-mPFC infusions of the D receptor agonist quinpirole, while another adolescent group received intra-mPFC infusions of the D antagonist amisulpride before defeat exposure. Results: Long-term decreases or increases in mPFC DA turnover were observed following adolescent or adult defeat, respectively. Adolescent defeat exposure elicits sustained increases in mPFC DA release, and DA turnover remains elevated beyond the stress experience before declining to levels below normal at P56. Activation of mPFC D receptors in nondefeated adolescents decreases DA activity in a similar manner to that caused by adolescent defeat, while defeat-induced reductions in mPFC DA activity are prevented by D receptor blockade. Conclusions: Both the developing and mature PFC DA systems are vulnerable to social stress, but only adolescent defeat causes DA hypofunction. This appears to result in part from stress-induced activation of mPFC D autoreceptors. [ABSTRACT FROM AUTHOR]

In the current study, microRNA (miRNA) microarrays were used to detect differentially expressed miRNAs in the myocardial tissues of rat models under stress, to screen target miRNA candidates for miRNA therapy of stress-induced myocardial injury. Rats were bound and suspended in order to induce acute stress (AS) and chronic stress (CS) models. miRNA microarrays were used to detect differentially expressed miRNA in the myocardial tissues of the stressed and control groups. In comparison to the normal control, there were 68 differentially expressed miRNAs in the AS model, of which 32 were upregulated and 36 were downregulated. There were 55 differentially expressed miRNAs in the CS model, of which 20 were upregulated and 35 were downregulated. Of the 123 miRNAs, 15 miRNAs were differentially expressed between the AS and CS groups, of which four were significantly upregulated (rno-miR-296, rno-miR-141, rno-miR-382 and rno-miR-219-5p) and 11 were downregulated (significantly downregulated, rno-miR-135a and rno-miR-466b). The stress of being bound and suspended induces myocardial injury in the rats. Myocardial injury may cause the differential expression of certain miRNAs. Psychological stress may lead to the significant upregulation of rno-miR-296, rno-miR-141, rno-miR-382 and rno-miR-219-5p in addition to the significant downregulation of miR-135a and miR-466b. [ABSTRACT FROM AUTHOR]

Most psychiatric disorders are characterized by emotional memory or learning disturbances. Chronic mild stress (CMS) is a common animal model for stress-induced depression. Here we examined whether 3 days of treatment using the CB1/2 receptor agonist WIN55,212-2 could ameliorate the effects of CMS on emotional learning (ie, conditioned avoidance and extinction), long-term potentiation (LTP) in the hippocampal-accumbens pathway, and depression-like symptoms (ie, coping with stress behavior, anhedonia, and weight changes). We also examined whether the ameliorating effects of WIN55,212-2 on behavior and physiology after CMS are mediated by CB1 and glucocorticoid receptors (GRs). Rats were exposed to CMS or handled on days 1-21. The agonist WIN55,212-2 or vehicle were administered on days 19-21 (IP; 0.5 mg/kg) and behavioral and electrophysiological measures were taken on days 23 and 28. The CB1 receptor antagonist AM251 (IP; 0.3 mg/kg) or the GR antagonist RU-38486 (IP; 10 mg/kg) were co-administered with WIN55,212-2. Our results show that CMS significantly modified physiological and behavioral reactions, as observed by the impairment in avoidance extinction and LTP in the hippocampal-accumbens pathway, and the alterations in depression-like symptoms, such as coping with stress behavior, weight gain, and sucrose consumption. The most significant effect observed in this study was that 3 days of WIN55,212-2 administration prevented the CMS-induced alterations in emotional memory (ie, extinction) and plasticity. This effect was mediated by CB1 receptors as the CB1 receptor antagonist AM251 prevented the ameliorating effects of WIN55,212-2 on extinction and LTP. The GR antagonist RU-38486 also prevented the CMS-induced alterations in extinction and plasticity, and when co-administered with WIN55,212-2, the preventive effects after CMS were maintained. The findings suggest that enhancing cannabinoid signaling could represent a novel approach to the treatment of cognitive deficits that accompany stress-related depression. [ABSTRACT FROM AUTHOR]

The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate the effect of an acute stressor on the variation of some physiological and immunological parameters of Siberian sturgeon (Acipenser baerii) juveniles. Fish, reared in 3 tanks for 10 weeks, were used for this study. The acute stress of fish consisted of 2 min of air exposure stress. Plasma levels of cortisol, glucose, and lactate as well as lysozyme activity in plasma were measured before stress and 1 hr, 3 hr, 6 hr, 9 hr, 12 hr, and 24 hr after stress. The plasma cortisol significantly increased in the highest level 1 hr after stress, yet it gradually declined after 3 hr. The glucose significantly increased only 1 hr after stress. There was no significant difference between plasma lactate prestress and poststress. Moreover, lysozyme activity was enhanced by stress, thus reaching the highest level 9 hr after stress. The results of this study indicate that Siberian sturgeon not only have a rapid response to acute stress, but also a great capacity for recovery from stress, thus returning physiological parameters to prestress levels after 6 hr. [ABSTRACT FROM PUBLISHER]

Stress can compromise welfare in any confined group of nonhuman animals, including those in shelters. However, an objective and practical method for assessing the stress levels of individual dogs housed in a shelter does not exist. Such a method would be useful for monitoring animal welfare and would allow shelters to measure the effectiveness of specific interventions for stress reduction. In this pilot study, activity levels were studied in 13 dogs using accelerometers attached to their collars. Behavioral stress scores as well as urinary and salivary cortisol levels were measured to determine if the dogs' activity levels while confined in the kennel correlated with behavioral and physiological indicators of stress in this population. The results indicated that the accelerometer could be a useful tool to study stress-related activity levels in dogs. Specific findings included a correlation between the salivary cortisol and maximum activity level (r= .62,p= .025) and a correlation between the urine cortisol-to-creatinine ratio and average activity level (r= .61,p= .028) among the study dogs. Further research is needed to better understand the complex relationship between stress and activity level among dogs in a kennel environment. [ABSTRACT FROM PUBLISHER]

As chronic stress is a significant risk factor for several cardiovascular disorders, this study investigated the hypothesis that long-term stress produced by crowding may lead to alterations in nitric oxide (NO) production and NO-dependent relaxation in the course of stress, resulting in endothelial dysfunction and hypertension in Wistar-Kyoto (WKY) rats. For this purpose, male WKY rats were divided into control (480 cm2/rat, four rats/cage, n = 8) and crowded (200 cm2/rat, five rats/cage, n = 10) groups for 8 or 12 weeks. Vasorelaxation was evaluated in vitro as a response to acetylcholine (ACh) of femoral arteries pre-contracted by serotonin, before and after NO synthase inhibition ( NG-nitro-l-arginine methyl ester, 300 μmol/l). Crowding increased plasma corticosterone concentration but failed to affect blood pressure (determined by tail-cuff plethysmography) of rats. NO production was unchanged in the hypothalamus and left ventricle of both stressed groups; however it was significantly elevated in the aorta. Maximal ACh-induced relaxation was elevated significantly after 8-week stress, but reduced after 12 weeks. Stress elevated the NO-dependent component and reduced the NO-independent component of ACh-induced relaxation in both crowded groups. However, a reduction in the NO-independent component was more pronounced after 12-week versus 8-week stress. In conclusion, elevated endothelium-dependent relaxation was observed after 8-week stress, while the extension of stress exposure resulted in a reduction in arterial relaxation associated with a more pronounced decrease of its NO-independent component. Thus, elevation of the NO-dependent component of relaxation can be considered as an adaptation mechanism, and impairment of NO-independent relaxation might be the initial step in chronic stress-induced cardiovascular disorders. [ABSTRACT FROM AUTHOR]