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• Witness social stress-induced cardiac remodeling was investigated in female rats. • Cardiomyocytes of stressed females showed defects in contractile properties and calcium dynamics. • Alterations in mechanisms regulating intracellular calcium transport were implicated. • Social stress-related pathophysiological processes can be studied in the female heart using the witness social stress model. The impact of psychosocial stressors on cardiovascular health in women is of growing interest in both the popular and scientific literature. Rodent models are useful for providing direct experimental evidence of the adverse cardiovascular consequences of psychosocial stressors, yet studies in females are scarce. Here, we investigated the effects of repeated exposure to witness social defeat stress (WS) on cardiomyocyte contractile function and intracellular Ca2+ homeostasis in young adult wild-type Groningen female rats. Female rats bore witness to an aggressive social defeat episode between two males for nine consecutive days or were exposed to a control procedure. Stress-related behaviors were assessed during the first and last WS/control exposure. Twenty-four hours after the last exposure, plasma corticosterone levels were measured, and cardiomyocytes were isolated for analyses of contractile properties and Ca2+ transients, and expression levels of proteins involved in intracellular Ca2+dynamics. The results show an impairment of the intrinsic cardiac mechanical properties and prolonged intracellular Ca2+decay in WS female rats showing social stress-related behavioral (larger amounts of burying behavior) and neuroendocrine (elevated plasma corticosterone levels) phenotypes. Further, the results implicate alterations in the sarcoplasmic reticulum Ca2+-ATPase/phospholamban complex in the contractile defects described in cardiomyocytes of WS female rats. In conclusion, this study highlights the utility of the WS model as an ethologically relevant social stressor for investigating pathophysiological processes that occur in the heart of female subjects and may increase vulnerability to social stress-related cardiovascular risk. [ABSTRACT FROM AUTHOR]

• Stress chemosignals partly improve emotional perspective taking in depressed individuals. • Stress chemosignals partly enhance affective responsiveness in depressed individuals. • Salivary cortisol levels remain unaffected by stress chemosignals. • Friendly-TSST chemosignals appear to have calming effects. Human body odors contain chemical signals that play a key role in our non-verbal communication regarding health, genetic identity, immune system, fitness, and emotional state. Studies on human chemosignaling in individuals with psychiatric diseases are scarce but indicate altered smell perception and emotion recognition in depressed individuals. In the present project, we aimed to investigate the influence of chemosensory substances in social stress sweat on emotion recognition, perspective taking, affective responsiveness as well as stress level in healthy and depressed individuals. Therefore, chemosensory stimuli (sweat samples from Trier social stress test (TSST) and friendly-TSST (fTSST)) were obtained from 39 healthy participants (19 females). In a next step, chemosensory stimuli and an odor-free blank (cotton pad) were used to stimulate another group of 40 healthy participants (20 females) and 37 individuals with depression (24 females). Those stimuli were examined regarding their influence on subjective feelings of stress, emotion perception and empathic reactions using an empathy test. Furthermore, physiological data (breathing, heart rate, skin conductance response, stress hormones) of the participants were collected during chemosensory stimulation. Depressed individuals improved their ability of perspective taking and affective responsiveness for the emotion grief when presented with stress chemosignals compared to no chemosignals. Healthy individuals remained unaffected regarding perspective taking and affective responsiveness. Both depressed and healthy individuals showed no increased stress hormone cortisol and α-amylase values during the social stress chemosignals condition, but reduced values for fTSST condition compared to no chemosignals respectively. The results imply that stress chemosignals do not trigger a stress reaction, but for depressed individuals they lead to a better emotion assessment for grief. This research contributes to a deeper understanding of the effects of social stress chemosignals on healthy and depressed individuals. Knowing the impact of human chemosignals on emotional processing is crucial for a better understanding of non-verbal human interaction. [ABSTRACT FROM AUTHOR]

• Inherent sociability has no major effect on coping with chronic social instability. • Chronic social instability stress induces higher arousal but not anhedonia. • Stressed females show higher monoaminergic levels with no turnover and decreases IDO and iNOs. • High sociable females present decreased IDO and NA and increased 5-HT and DA. • Chronic social instability stress does not elicit an allostatic load. Extensive literature has reported a link between social stress and mental health. In this complex relationship, individual strategies for coping with social stress are thought to have a possible modulating effect, with sociability being a key factor. Despite the higher incidence of affective disorders in females and sex-related neurochemical differences, female populations have been understudied. The aim of the present study was, therefore, to analyze the behavioral, neuroendocrine, and neurochemical effects of stress in female OF1 mice, paying special attention to social connectedness (female mice with high vs low sociability). To this end, subjects were exposed to the Chronic Social Instability Stress (CSIS) model for four weeks. Although female mice exposed to CSIS had increased arousal, there was no evidence of depressive-like behavior. Neither did exposure to CSIS affect corticosterone levels, although it did increase the MR/GR ratio by decreasing GR expression. Female mice exposed to CSIS had higher noradrenaline and dopamine levels in the hippocampus and striatum respectively, with a lower monoaminergic turnover, resulting in an increased arousal. CSIS increased serotonin levels in both the hippocampus and striatum. Similarly, CSIS was found to reduce kynurenic acid, 3-HK, and IDO and iNOS enzyme levels in the hippocampus. Interestingly, the observed decrease in IDO synthesis and the increased serotonin and dopamine levels in the striatum were only found in subjects with high sociability. These highly sociable female mice also had significantly lower levels of noradrenaline in the striatum after CSIS application. Overall, our model has produced neuroendocrine and neurochemical but not behavioral changes, so it has not allowed us to study sociability in depth. Therefore, a model that induces both molecular and behavioral phenotypes should be applied to determine the role of sociability. [ABSTRACT FROM AUTHOR]

• Hamsters show sex differences in the formation of dominance relationships. • Dominance relationships are less stable in female compared to male hamsters. • Dominance status creates sex differences in status-dependent neural plasticity. Dominance relationships are identified by changes in agonistic behavior toward specific individuals. While there are considerable individual and species differences in dominance relationships, sex differences are poorly understood in rodent models because aggression among female rodents is rare. The aim of this study was to characterize sex differences in the formation and maintenance of dominance relationships in same-sex pairs of male and female Syrian hamsters. We pooled data from multiple projects in our lab to evaluate dominance interactions in 68 male dyads and 88 female dyads. In each project, animals were matched with a partner similar in age, sex, and estrous cycle and we exposed animals to daily social encounters for two weeks in a resident-intruder format. We found that female hamsters were quicker to attack and attacked at higher rates compared to males regardless of dominance status. In addition, resident female hamsters were quicker to attack and attacked at higher rates than intruder females, but aggression in males did not depend on residency status. Female subordinates were quicker to submit and fled at higher rates from their dominant counterparts compared to male subordinates. Intruder subordinate females were quicker to submit and fled at higher rates than resident subordinate females. Females were also more resistant than males to becoming subordinate in that they fought back more consistently and were more likely to reverse their dominance status. These findings indicate that dominance relationships are less stable in females compared to males and that residency status has a larger impact on agonistic behavior in females than males. Overall, differences in how males and females display territorial aggression can lead to sex differences in the establishment and maintenance of dominance relationships. [ABSTRACT FROM AUTHOR]

Although Syrian hamsters are thought to be naturally solitary, recent evidence from our laboratory demonstrates that hamsters may actually prefer social contact. Hamsters increase their preference for a location associated with an agonistic encounter regardless of whether they have “won” or “lost”. It has also been reported that social housing as well as exposure to intermittent social defeat or to a brief footshock stressor increase food intake and body mass in hamsters. By contrast, it has also been suggested that housing hamsters in social isolation causes anxiety-induced anorexia and reductions in body mass selectively in females. The purpose of this study was to determine the physiological consequences of housing hamsters in social isolation versus in social groups. Male and female hamsters were housed singly or in stable groups of 5 for 4 weeks after which they were weighed and trunk blood was collected. In addition, fat pads and thymus and adrenal glands were extracted and weighed. Serum and fecal cortisol were measured using an enzyme-linked immunoassay. Housing condition had no effect on serum or fecal cortisol, but socially housed hamsters displayed modest thymus gland involution. Socially housed females weighed more than did any other group, and socially housed females and males had more fat than did socially isolated hamsters. No wounding or tissue damage occurred in grouped hamsters. Overall, these data suggest that Syrian hamsters tolerate both stable social housing and social isolation in the laboratory although social housing is associated with some alteration in stress-related and bioenergetic measures. [ABSTRACT FROM AUTHOR]

Repeated exposure to psychosocial stress is a robust sympathomimetic stressor and as such has adverse effects on cardiovascular health. While the neurocircuitry involved remains unclear, the physiological and anatomical characteristics of the locus coeruleus (LC)-norepinephrine (NE) system suggest that it is poised to contribute to stress-induced cardiovascular vulnerability. A major theme throughout is to review studies that shed light on the role that the LC may play in individual differences in vulnerability to social stress-induced cardiovascular dysfunction. Recent findings are discussed that support a unique plasticity in afferent regulation of the LC, resulting in either excitatory or inhibitory input to the LC during establishment of different stress coping strategies. This contrasting regulation of the LC by either afferent regulation, or distinct differences in stress-induced neuroinflammation would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The goal of this review is to highlight recent developments in the interplay between the LC-NE and cardiovascular systems during repeated stress in an effort to advance therapeutic treatments for the development of stress-induced cardiovascular vulnerability. [ABSTRACT FROM AUTHOR]

There is information indicating that the variations induced by the menstrual cycle may influence the capacity of young women to respond to stress. The physiological response to stress changes across the stages of the lifespan; however, in spite of the great increase in life expectancy, the way women react after menopause, a period characterized by a dramatic decline in sex hormones, has not been sufficiently studied. The main objective of the study was to examine the capacity to respond to and recover from an acute social stressor in post-menopausal women compared to young women. The second objective was to investigate the consequences of behavior on the self-regulatory systems. We measured behavior, cortisol, and heart rate during a speaking task in front of a committee in sixty-seven women: 36 post-menopausal and 31 pre-menopausal (follicular group n = 14; luteal group n = 17). No differences in heart rate reactivity between three groups were found. Post-menopausal women showed less cortisol reactivity to stress; they also displayed a higher percentage of Gestures during the speaking task, reflecting a clearer pattern of active coping compared to the young women. In post-menopausal women, behaviors that reflect active coping strategies were related to better autonomic regulation. By contrast, in pre-menopausal women, cortisol changes seemed to be modulated by passive and reactive behaviors such as Submission and Assertion. These results emphasize the importance of considering age and Hormonal Status in coping processes, including reactivity and recovery from stressful situations. [ABSTRACT FROM AUTHOR]

The way how individuals respond to chronic challenges can vary tremendously, and such differences are closely linked to personality. The few available studies on individual differences in stress-related immunosuppression in non-human mammals have been mainly carried out with laboratory strains. We conducted a study in male mound-building mice ( Mus spicilegus ) of wild origin. We distinguished between high (HAN) and low anxious/neophobic (LAN) personality types, quantified by subjects' consistent and associated behavioral responses in repeated elevated plus maze and novel object tests. After reaching maturity, parts of the subjects were regularly confronted to different resident pairs over a period of 5 days to provoke a condition of chronic social stress, while others were used as untreated controls. We measured fecal corticosteroid metabolite (FCM) concentrations and different cellular immune parameters from blood and spleen. Socially confronted HAN showed higher increases in FCM concentrations than LAN, indicating a more pronounced physiological stress response in the former personality type. HAN of the experimental group also showed lower percentages of effector T cells (Teff) and higher regulatory T cells (Treg) in the spleen; the latter are known for their immunosuppressive activity. Considering the ratio of Teff/Treg, animals with higher increases in FCM concentrations during the late period of the experiment showed a stronger shift towards Treg cells, supporting immunosuppressive effects of chronically elevated corticosteroid levels. Summarizing, our results strongly suggest that immunomodulatory effects of socially induced stress were altered by individual differences in anxiety/neophobia, emphasizing the significance of personality in shaping physiological responses to challenge. [ABSTRACT FROM AUTHOR]

Rainbow trout ( Oncorhynchus mykiss ) confined in pairs form social hierarchies in which distinctive behavioural and physiological phenotypes distinguish dominant from subordinate fish. In particular, subordinate fish are characterized by inhibition of behaviours such as feeding and activity, by low growth rates, and by chronic elevation of circulating glucocorticoid stress hormone (cortisol) concentrations. To evaluate the ability of trout to recover from chronic social stress, pairs of fish were allowed to interact for 4 d, and subordinate fish were then separated from dominant fish. Recovery was assessed using behavioural (position in the tank, latency to feed, and food consumed) and physiological (plasma cortisol and glucose concentrations, liver glycogen content, hepatosomatic index, specific growth rate, and gall bladder mass) indices. During 48 or 96 h of recovery from the 4 d interaction period, only plasma cortisol and glucose levels of subordinates returned to baseline values consistent with those of dominant and sham trout (fish that were handled like paired fish but housed singly). All other physiological variables failed to recover, likely owing to the absence of behavioural recovery, including continued inhibition of food intake even following separation from the dominant fish. Whereas subordinate fish exhibited an attenuated cortisol response to an acute netting stressor, ‘recovered’ subordinates mounted a cortisol response that was equivalent to those of dominant and sham fish. However, ‘recovered’ subordinates that were paired with a socially naïve conspecific were unable to achieve non-subordinate status. Collectively, these results indicate that recovery of the cortisol response precedes behavioural recovery from social subordination. [ABSTRACT FROM AUTHOR]

The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (> 4 weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4 weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders. [ABSTRACT FROM AUTHOR]

Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short- and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE + STRESS: mice housed in EE and submitted to social stress (n = 32); 2) EE + NO STRESS: mice housed in EE without stress (n = 32); 3) SE + STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n = 32); and 4) SE + NO STRESS (n = 32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE + STRESS group displayed significantly higher corticosterone levels than EE + NO STRESS group whereas EE + NO STRESS group showed lower levels than SE + NO STRESS. On PND 83, Phase II of the study began. Animals (n = 96) were assigned to two different housing conditions: EE (n = 48) and SE (n = 48). On PND 112, corticosterone analysis (n = 32) and behavioral study (n = 64) were done. The factor “Housing Phase II” reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that “Initial Housing” condition was significant: animals allocated in EE during Phase I of the study showed higher corticosterone levels, lower body weight and higher fluid intake than SE mice. “Initial Stress” had significant long-term actions on food intake and exploratory behavior: animals initially reared under stress conditions displayed higher food intake and lower exploration levels on the hole-board test than non-stressed mice. In the elevated plus-maze, there were significant interactions between factors “Initial Housing” and “Initial Stress”. These factors did not reach statistical significance for motor activity or learning task. We can conclude that both short- and long-term effects of housing conditions are evident for corticosterone levels, body weight and fluid intake. Social stress induced short-term effects on body weight, food and fluid intake and exploratory behavior whereas long-acting effects were reflected on food intake and exploratory behavior. Further studies are needed in order to explore more in depth behavioral and physiological consequences of social stress and environmental enrichment. [ABSTRACT FROM AUTHOR]

Environmental factors acting during development of an individual may influence future health and disease susceptibility. Stressors, including altered diet, psychosocial stress, and immune challenge, during gestation can have negative consequences on the intrauterine environment and increase disease susceptibility of the developing fetus. The long-term effects on offspring have been observed in humans and include greater susceptibility to psychiatric disease, such as depression and anxiety disorders, and adverse metabolic conditions including obesity, diabetes and cardiovascular disease. Studies in my laboratory use rodent models and incorporate a multilevel approach to determine the behavioral, physiological, and neurobiological correlates of disease development as a consequence of early life stressors. The road I took in developing this research program was a rather circuitous one and navigating that path would not have been possible without the many mentors, colleagues, fellows and students who provided critical support. Although my name appears on the plaque of the Alan N. Epstein Research Award, I share this with all those I had the privilege of working with along that road, as briefly summarized in this article. [ABSTRACT FROM AUTHOR]

Background Heart failure (HF) prognosis is negatively influenced by adverse environmental conditions associated with psychological distress and depression. The underlying mechanisms are not well understood because of insufficient experimental control in prior clinical and epidemiological studies. Using a validated animal model we examined whether distress-producing environmental manipulations (social isolation and crowding) increase HF progression following myocardial infarction (MI). Methods MI was induced using coronary artery ligation in 8-week old male Wistar rats (N = 52) and results were compared to sham surgery (N = 24). Housing conditions were randomly assigned at 5 days post MI or sham surgery (1/cage = isolation, 2/cage = standard reference condition, or 4/cage = crowding) and continued for 17 weeks until the end of observation. The open field test was used to test behavioral responses. Echocardiograms were obtained at weeks 8 and 16, and left ventricular (LV) weight at week 17. Results Housing conditions increased behavioral markers of distress (p = 0.046) with the strongest effects for the isolated (1/cage) (p = 0.022). MI did not increase distress-related behaviors compared to sham. MI-surgery resulted in characteristic HF indices (left ventricular ejection fraction (LVEF) at week 16 = 46 ± 12% vs. 80 ± 7% in sham, p < 0.001). Housing condition was not related to LVEF or LV weight (p > 0.10). Conclusions Adverse environmental conditions, particularly isolated housing, produce increases in some of the behavioral indicators of distress. No effects of housing were found on post-MI progression of HF. The distress–HF associations observed in humans may therefore reflect common underlying factors rather than an independent causal pathway. Stronger environmental challenges may be needed in future animal research examining distress as related HF progression. [ABSTRACT FROM AUTHOR]

Recent research suggests that cortisol (C) level moderates testosterone (T) reactivity to the Trier Social Stress Test (TSST) in men. The extent to which C moderates T reactivity in other circumstances and in women is not known. In this retrospective study, before- and after-competition salivary levels of C and T from 97 intercollegiate women athletes competing in one of four different sports (soccer, volleyball, softball, tennis) were used to evaluate the influence of before-competition C level on T reactivity in women's athletic competition. Athletic competition was associated with a substantial increase in salivary levels of C and T in the vast majority of athletes. Before-competition level of C significantly moderated testosterone reactivity to athletic competition — women with relatively low levels of C showed larger increases in T to competition than women with higher levels of C. Clearly, the moderating effect of C on T reactivity is not limited to laboratory settings intended to increase social stress, but is also seen in (as we show here) the context of athletic competition. [ABSTRACT FROM AUTHOR]

The modulation of risk-taking is critical for adaptive and optimal behavior. This study examined how oxytocin (OT) and arginine vasopressin (AVP) influence risk-taking in function of three parameters: sex, risk-valence, and social context. Twenty-nine healthy adults (14 males) completed a risk-taking task, the Stunt task, both in a social-stress (evaluation by unfamiliar peers) and non-social context, in three separate drug treatment sessions. During each session, one of three drugs, OT, AVP, or placebo (PLC), was administered intra-nasally. OT and AVP relative to PLC reduced betting-rate (risk-averse effect). This risk-averse effect was further qualified: AVP reduced risk-taking in the positive risk-valence (high win-probability), and regardless of social context or sex. In contrast, OT reduced risk-taking in the negative risk-valence (low win-probability), and only in the social-stress context and men. The reduction in risk-taking might serve a role in defensive behavior. These findings extend the role of these neuromodulators to behaviors beyond the social realm. How the behavioral modulation of risk-taking maps onto the function of the neural targets of OT and AVP may be the next step in this line of research. [ABSTRACT FROM AUTHOR]

Abstract: Anorexia and anxiety cause significant mortality and disability with female biases and frequent comorbidity after puberty, but the scarcity of suitable animal models impedes understanding of their biological underpinnings. It is reported here that in adult or weanling Syrian hamsters, relative to social housing (SH), social separation (SS) induced anorexia characterized as hypophagia, weight loss, reduced adiposity, and hypermetabolism. Following anorexia, SS increased reluctance to feed, and thigmotaxis, in anxiogenic environments. Importantly, anorexia and anxiety were induced post-puberty with female biases. SS also reduced hypothalamic corticotrophin-releasing factor mRNA and serum corticosteroid levels assessed by RT-PCR and RIA, respectively. Consistent with the view that sex differences in adrenal suppression contributed to female biases in anorexia and anxiety by disinhibiting neuroimmune activity, SS elevated hypothalamic interleukin-6 and toll-like receptor 4 mRNA levels. Although corticosteroids were highest during SH, they were within the physiological range and associated with juvenile-like growth of white adipose, bone, and skeletal muscle. These results suggest that hamsters exhibit plasticity in bioenergetic and emotional phenotypes across puberty without an increase in stress responsiveness. Thus, social separation of hamsters provides a model of sex differences in anorexia and anxiety during adulthood and their pathogeneses during adolescence. [Copyright &y& Elsevier]

Abstract: Social subjugation has widespread consequences affecting behavior and underlying neural systems. We hypothesized that individual differences in stress responsiveness were associated with differential expression of neurotrophin associated genes within the hippocampus and amygdala. To do this we examined the brains of hamsters placed in resident/intruder interactions, modified by the opportunity to escape from aggression. In the amygdala, aggressive social interaction stimulated increased BDNF receptor TrKB mRNA levels regardless of the ability to escape the aggressor. In contrast, the availability of escape limited the elevation of GluR1 AMPA subunit mRNA. In the hippocampal CA1, the glucocorticoid stress hormone, cortisol, was negatively correlated with BDNF and TrKB gene expression, but showed a positive correlation with BDNF expression in the DG. Latency to escape the aggressor was also negatively correlated with CA1 BDNF expression. In contrast, the relationship between amygdalar TrKB and GluR1 was positive with respect to escape latency. These results suggest that an interplay of stress and neurotrophic systems influences learned escape behavior. Animals which escape faster seem to have a more robust neurotrophic profile in the hippocampus, with the opposite of this pattern in the amygdala. We propose that changes in the equilibrium of hippocampal and amygdalar learning result in differing behavioral stress coping choices. [Copyright &y& Elsevier]

Abstract: Adverse social environments play a relevant role in the onset and progression of mood disorders. On the other hand, depression is an independent risk factor for cardiovascular morbidity. This study was aimed at (i) corroborating the validity of a rat model of depression based on a negative social episode followed by social isolation and (ii) verifying its impact on cardiac function and structure. Pair housed, wild-type Groningen rats (Rattus norvegicus) were implanted with radiotransmitters for ECG, temperature and activity recordings. They were either exposed to a social defeat episode followed by 4-week isolation or left undisturbed with their female partners. The social challenge induced a series of biological changes that are commonly taken as markers of depression in rats, including decreased body weight gain and reduced preference for sucrose consumption, functional and structural changes of the hypothalamic–pituitary–adrenocortical axis, increased anxiety in the elevated plus maze test. The cardiovascular alterations consisted in (i) transitory heart rate circadian rhythm alterations, (ii) lack of habituation of cardiac autonomic responsivity (tachycardia and vagal withdrawal) to an acute stressor, and (iii) moderate hypertrophy affecting the right ventricle of the heart. These results indicate that a depression-like state induced via this model of social challenge was associated with a few modest cardiovascular changes. Further studies are required to confirm the validity of this rat model of depression as a valid preclinical approach to the comprehension of the biological substrates underlying depression–cardiovascular comorbidity. [Copyright &y& Elsevier]

Abstract: Male Syrian hamsters are naturally aggressive animals that reliably defend their home territory against intruding conspecifics. Hamsters that lose agonistic encounters subsequently exhibit a striking change in their agonistic behavior, however, expressing no aggression and instead becoming highly submissive, a behavioral change that we have termed conditioned defeat. We have generally employed an inescapable defeat training protocol when studying conditioned defeat. The purpose of the present study was to determine if conditioned defeat is an epiphenomenon of the inescapable defeat experience by comparing the behavior of hamsters exposed to inescapable versus escapable defeat. In the conditioned defeat model, defeated hamsters subsequently generalize their submission and social avoidance to a novel, non-aggressive opponent, suggesting that hamsters subjected to inescapable defeat may not form a specific memory of their aggressive opponent. Thus, a secondary purpose of the present study was to determine whether hamsters subjected to our defeat protocol have the ability to recognize a familiar opponent following defeat. Our results provide evidence that conditioned defeat is not solely a by-product of inescapable defeat because all experimental animals, regardless of the type of defeat, expressed conditioned defeat during testing. We also found that animals experiencing an inescapable defeat avoided a familiar aggressor significantly more than they did an unfamiliar aggressor, demonstrating that these animals have the ability to recognize their previous attacker. Thus, we maintain that a variety of social defeat models, and conditioned defeat in particular, represent generalizable and ethologically valid models with which to study the effects of social stress on physiology and behavior. [Copyright &y& Elsevier]

Abstract: Chronic psychosocial stress triggers cardiovascular diseases although underlying mechanisms are still elusive. This study examined the effect of social stress on cardiomyocyte contractile function and pathological changes in myocardium using the visible burrow system (VBS) model. Chronic social stress was induced using a mixed-sex VBS housing in adult Sprague–Dawley (SD) rats. Contractile and intracellular Ca2+ properties were evaluated in isolated cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), maximal velocity of shortening/relengthening (± dL/dt), Fura-2 fluorescence intensity, and intracellular Ca2+ decay. Myocardial histology was evaluated using Masson trichrome staining. Social stress led to depressed PS, ± dL/dt, shortened TPS and prolonged TR90 compared with the unstressed controls. Baseline and electrically-stimulated rise in Ca2+ were reduced whereas intracellular Ca2+ decay was delayed in stressed rats. Histological analyses exhibited overt interstitial fibrosis and cardiomyocyte hypertrophy in stressed rats. The GSH/GSSG ratio (indicative of oxidative stress status) was reduced whereas oxidative protein carbonyl formation was elevated in stressed rats. Western blot analysis showed unchanged expression of superoxide dismutase 1 (SOD1), β1-adrenoceptor (β1-AR) levels, reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) levels, and elevated phosphorylation of the stress signaling protein kinase JNK but not ERK in myocardium from stressed rats. Short-term in vitro treatment of cardiomyocytes with the stress inducer phenylephrine mimicked cell damage and intracellular Ca2+ mishandling, the effects of which were mitigated by antioxidant, JNK inhibition, carvedilol and SERCA2a adenovirus. These findings indicate that chronic social stress is detrimental to cardiac structure and function possibly via mechanisms associated with oxidative injury and intracellular Ca2+ mishandling. [Copyright &y& Elsevier]

Abstract: Social interactions in rodents are rewarding and motivating and social isolation is aversive. Accumulating evidence suggests that disruption of the social environment in adolescence has long-term effects on social interactions, on anxiety-like behavior and on stress reactivity. In previous work we showed that adolescent isolation produced increased reactivity to acute and to repeated stress in female rats, whereas lower corticosterone responses to acute stress and decreased anxiety-related behavior were noted in isolated males. These results indicate a sex specific impact on the effects of social stress in adolescence. However, little is known about whether social isolation impacts behaviors related to affect and whether it does so differently in male and female rats. The present study investigated the impact of adolescent social isolation from day 30–50 of age in male and female Sprague Dawley rats on behavior in the forced swim test at the end of adolescence and in adulthood and on behavior in the sucrose preference test in adulthood. Adult female rats that were isolated in adolescence exhibited increased climbing on the first and second day of the forced swim test and showed an increased preference for sucrose compared to adult females that were group-housed in adolescence. There were no effects in male rats. The results indicate that social isolation in adolescence produces a stable and active behavioral phenotype in adult female rats. [Copyright &y& Elsevier]

Abstract: In many mammal species, reproduction is not shared equally among the members of a social unit. Even though reproductive skew seems unlikely in females of solitary species, this phenomenon could result from environmental factors. Although solitary in the wild, captive Syrian hamsters (Mesocricetus auratus) are generally housed in groups. We investigated whether social stress produces some degree of reproductive skew in this solitary species and whether female reproductive success varies as a function of social rank. To assess the physiological relationship between social stress and fertility, we monitored reproductive hormones and glucocorticoids of solitary and pair-housed females during pregnancy by means of recently established non-invasive methods for measuring hormone metabolites in the feces. The patterns of fecal progesterone, estrogen and glucocorticoid metabolites were similar to those found in blood and reported in the literature for pregnant hamsters. As expected, dominant females had higher breeding success than subordinate females. However the rate of reproductive failure was also very high among the singly housed females of our control group. The number of pups per litter, the average sex-ratio in each group, and the mean weight of pups did not differ significantly among groups. Glucocorticoid concentrations were unaffected by housing and social rank and the few differences between the endocrine profiles of singly- and pair-housed females are not sufficient to explain the observed difference in breeding success. It is likely that social isolation impairs reproduction in the same manner as subordination. Our findings suggest that social isolation of animals accustomed to group living was equally as disturbing as cohabitation with an unknown conspecific. [Copyright &y& Elsevier]

Abstract: Stress is known to elevate core body temperature (CBT). We recorded CBT in a diurnal animal, the male tree shrew, during a one-week control period and a one-week period of social stress using a telemetric system. During the stress period, when animals were confronted with a dominant male for about 1h daily, CBT was increased throughout the day. We analyzed CBT during the night when animals were left undisturbed and displayed no locomotor activity. To determine whether nocturnal hyperthermia may be related to stress-induced changes in hormonal status, we measured testosterone, noradrenalin and cortisol in the animals'' morning urine. The daily social stress increased the mean nocturnal temperature by 0.37°C. Urinary testosterone was reduced during the stress period, and there was a significant negative correlation between testosterone and the area under the curve (AUC) of the nocturnal CBT. This means that stress-induced hyperthermia was strongest in the animals with the lowest testosterone concentrations. As expected, urinary noradrenalin was elevated during the stress week but a positive correlation with the AUC data was only found for animals younger than 12months. Cortisol was also increased during the stress week but there were no correlations with nocturnal hyperthermia. However, the stress-induced increases in noradrenalin and cortisol correlated with each other. Furthermore, there were no correlations between the stress-induced increase in nocturnal CBT and body weight reduction or locomotor activity during the light phase. Interestingly, the extent of nocturnal hyperthermia depended on the animals'' ages: In animals younger than 12months, stress increased the AUC by 48%, in animals aged between 12 and 24months, stress increased the AUC by 36%, and older animals showed only a 7% increase. However, testosterone was not significantly reduced in the older animals. The present data reveal an interrelation between the extent of stress-induced nocturnal hyperthermia, the animals'' gonadal hormone status and their ages. The negative correlation between hyperthermia and testosterone indicates that this hormone in particular plays an important role in the regulation of body temperature in male tree shrews. [Copyright &y& Elsevier]

Abstract: Stress of social defeat in rodents is known to have a strong and long-lasting effect on brain, physiology and behavior, which bears similarities with certain human stress related psychopathologies. Previous experiments in this lab showed that social defeat stress suppresses testosterone secretion and causes a lasting desensitization of the serotonergic 5-HT1A receptors. Testosterone supplementation in socially stressed tree shrews prevented a decrease in hippocampal 5-HT1A receptor binding. These receptors are hypothesized to play an important role in neurogenesis in this brain structure. We designed the present experiment to test if social defeat reduces hippocampal cell proliferation and neurogenesis in rats and if testosterone supplementation can prevent this reduction. The results indicate that repeated social defeat stress on 5 successive days induces a significant drop in plasma testosterone levels in male rats and suppresses hippocampal cell proliferation 24h and 3weeks after the end of the stress period. Testosterone supplementation prevented the social stress induced drop in plasma testosterone levels. The hormone supplementation also reduced the negative effect of stress on hippocampal BrdU labeling at 3weeks post-defeat. This effect was, however, rather weak and was caused by the tendency of the hormone in itself to suppress proliferation and the failure to fully recover the proliferation rate. Survival of dentate gyrus cells that either proliferated prior to the stress period or 24h after the last defeat was not affected by the social defeats. Thus the stress-induced lowering of hippocampal cell proliferation is not likely to be caused by transient inhibition of testosterone secretion during social stress. [Copyright &y& Elsevier]

Abstract: There is increasing evidence that adolescence, like early life, is a sensitive period in which ongoing brain development can be influenced by environmental factors. This review describes our use of social instability as a model of mild adolescent social stress, its effects on social interactions and on hypothalamic–pituitary–adrenal function over the course of the procedure and in response to new stressors. The effects of social instability are sex-specific, with qualitative differences between the sexes on HPA function over the course of the stressor procedure, and with greater effects in males on behaviour observed during the social instability and greater effects in females on behavioural responses to drugs of abuse into adulthood, long after the stress exposure. The results from investigations with this model of adolescent social stress are discussed in relation to those of studies using other stressor procedures. Elevated exposure to glucocorticoids over the course of adolescence confers sex-specific changes in behavioural responses to drugs of abuse, which may be of relevance for understanding risk factors in people. [Copyright &y& Elsevier]

Abstract: Peer victimization in the form of bullying is a chronic social stressor experienced by many humans during development. Exposure to bullying has been associated with a variety of mental disorders, such as anxiety and depression. Participants pre-selected for the presence or absence of a history of being bullied were brought into a laboratory and placed in a stressful situation. Blood pressure, heart rate, and salivary cortisol levels were measured before the introduction of the stressor (Time 1), at the end of the stressor (Time 2), and after its removal (Time 3). Men with a history of exposure to frequent bullying showed blunted blood pressure responses at Time 2 compared to control men. Bullied and Non-bullied women did not show any differences in any of the measures. Men and women in both groups showed an increase in heart rate in response to the stressor. There were no significant differences in salivary cortisol levels between Bullied and Non-bullied participants. However, salivary cortisol levels and systolic blood pressure were lower in Bullied male participants who reported having no feelings of anger about their experience compared to controls and those who did report anger. These data show altered sympathetic responses to stress in men with a history of victimization as well as suggesting long-term effects on the HPA axis in the most affected individuals. [Copyright &y& Elsevier]

Abstract: We studied levels of fecal glucocorticoid metabolites (GCM) in a social rodent — Egyptian spiny mouse. As breeding adults are socially dominant over subadults, and adolescent males are driven away by the dominant males, we addressed the question whether animals within extended families are stressed differently depending upon their social category. In addition, we evaluated whether there are differences between non-commensal (outdoor) and commensal (adapted to human settlements) populations. Concentrations of fecal GCM were assessed from samples collected in a special cage that allowed continuous individual sampling of undisturbed mice housed as a semi-natural social unit. First we performed an ACTH challenge test to validate two enzyme immunoassays (EIA): a 5α-pregnane-3β,11β,21-triol-20-one EIA and an 11-oxoetiocholanolone EIA to measure a group of fecal GCM in this species. Next we monitored concentrations of fecal GCM in 68 individuals belonging to 10 family groups and two populations. Commensal spiny mice showed higher fecal GCM levels than non-commensal ones. No effect of age (i.e., social dominance) and only a small effect of sex (in the commensal population only, with males exhibiting lower values) on fecal GCM levels were found. On the other hand, considerable variations in measured fecal GCM between family groups were revealed, indicating that the social settings of the particular group play an important role. [Copyright &y& Elsevier]

Abstract: KINSEY, S. G., BAILEY, M. T., SHERIDAN, J. F., PADGETT, D. A. The inflammatory response to social defeat is increased in older mice. PHYSIOL BEHAV 91(0) 000-000, 2007. Previous research indicates that repeated social defeat of mice causes increased lymphocyte trafficking to the spleen, elevated proinflammatory cytokine production, and induced glucocorticoid insensitivity in splenocytes. Social defeat also causes increases in anxiety-like behavior. This study investigated whether repeated social defeat results in similar immunoregulatory and behavioral changes in older mice as those seen previously in young adult mice. The data revealed that, regardless of age, defeated mice had significantly more splenic CD11b+ Gr-1+ monocytes and neutrophils than controls. Supernatants harvested from cultured splenocytes from older mice contained comparatively higher IL-6 and TNF-α than supernatants from younger animals. In addition, those same cells derived from older defeated mice were hypersensitive to lipopolysaccharide (LPS) and insensitive to glucocorticoids in vitro. As seen previously in young adult mice, social defeat caused an increase in anxiety-like behavior in the open field test, but had no effect on learned helplessness in the forced swim test. These data indicated that repeated social defeat results in a proinflammatory state that is exacerbated in older mice. The implications of these data are noteworthy, given the strong role of inflammation in many age-related diseases. [Copyright &y& Elsevier]

Abstract: The aim of this study was to develop an animal model of major depression. Since two thirds of depressive patients are women, it is important to develop specific female animal models of depression. We therefore determined the consequences of chronic social defeat in individually housed prepubertal female pigs confronted with a dominant, older pig. Repeated defeat increased the salivary cortisol level, measured immediately after the confrontations, but this effect diminished after repeated confrontations. Neither organ weights nor the number of glucocorticoid (GR) and mineralocorticoid (MR) receptors in the ventral hippocampus were affected by repeated defeat. Serotonin turnover in the dorsal hippocampus was also unaffected. Behavioral analysis revealed that across confrontations, the pigs reduced the time spent actively attacking the dominant pigs, whereas the time increased in which the pigs passively underwent aggression and/or actively avoided aggression. Therefore, we conclude that the repeated social defeat paradigm does not induce long-lasting depression-like neuroendocrine effects as a consequence of behavioral adaptations (changes in the fighting strategy) in the young female pigs. [Copyright &y& Elsevier]

Abstract: Bank vole pups produce ultrasounds when isolated from the nest, as other rodents do. The present study was intended to elucidate the possible interaction between the social stress of isolation from the mother and the physical stress of low ambient temperature during the nesting period. Although bank vole pups removed from nests and monitored at nest temperature vocalized at high frequency, the number and duration of signals increased at lower ambient temperature. In the tested voles it appears that exposure to cold was the most important stimulus of vocalization during the preweaning period. This effect can be enhanced by prolonged isolation from the mother, manifested as longer duration of calls. Moreover, vocalization was reduced not only by the odor from the home nest, but also by exposure to bedding of an alien lactating bank vole or even a lactating mouse fed the same diet. This suggests that the olfactory signals affecting the ultrasonic vocalization of bank vole pups probably are a mixture of volatile metabolites related to the physiological status and diet of rodent females. The reported experiments provide convincing evidence that the vocalization of bank vole pups is affected by isolation from the mother, by ambient temperature, and by olfactory signals released by lactating rodent females. [Copyright &y& Elsevier]

Abstract: The removal of individuals from social groups, e.g. in order to maintain appropriate stocking densities in groups of rapidly growing young laboratory rats, is often necessary. However, such removals may be stressful and few studies have investigated their effects on the behaviour, physiology and welfare of the remaining group members. In this study we investigated this issue for rats housed at different stocking densities by observing behaviour and recording faecal corticosterone metabolite levels both before and after removal. We found that, irrespective of stocking density, the rats remaining in the home cage significantly increased agonistic behaviour, audible vocalization, aggressive grooming, bar-chewing and climbing behaviour following removal of their cage-mates, and that these behavioural changes were associated with a highly significant post-removal increase in their faecal corticosterone metabolite levels. Taking the behavioural and physiological results together, it appears that the removal of individuals from groups of young laboratory rats resulted in social stress, and thus an apparent impairment of welfare. [Copyright &y& Elsevier]

Abstract: Social affiliation–avoidance behaviors are essential indices of sociality. We examined changes in social affiliation–avoidance behaviors in an open-field apparatus while simultaneously measuring wheel-running activity. Recent studies suggest that mice increase wheel-running activity in stressful situations; thus, we hypothesized that wheel-running activity would reflect a state of social stress and avoidance. Mean duration of wheel-running increased significantly when mice were confronted with unfamiliar mice compared to cage mates. There were negative correlations between the amount of wheel-running and social affiliation indices. We also examined the effect of social defeat on wheel-running activity. Mice that had experienced social defeat significantly increased their wheel-running when an aggressor mouse was present. This social defeat-induced wheel-running activity was ameliorated by the administration of diazepam. Our results indicate that wheel-running activity is relevant to social affiliation–avoidance behaviors and may be a reliable index of anxiety induced by social stress. [Copyright &y& Elsevier]

Abstract: Adolescence has been described as an important period to acquire social competences required for adult life. It has been suggested that early stress experiences could affect the development of the brain at different levels. These changes in the brain during adolescence may be related with the development of psychopathologies such as depression and social anxiety in adulthood. In the first experiment, we examined long-term effects of repeated social stress during adolescence on adult social approach–avoidance behavior. For that purpose, adolescent male Wistar rats were exposed twice at postnatal day (Pnd) 45 and Pnd48 to the resident–intruder paradigm followed by three times psychosocial threat with the same resident. Three weeks after the last psychosocial threat experience the animals were behaviorally tested in a social approach–avoidance test. Socially stressed animals spent less time in the interaction zone with an unfamiliar male adult rat. These data suggest that animals exposed to social stress during adolescence show a higher level of social anxiety in adulthood. In the second experiment, we investigated whether these long-term effects of social stress during adolescence on behavior draw a parallel with changes in brain monoamine content, biosynthesis and turnover. Using the same experimental design as in the first experiment, HPLC analysis of various brain regions showed that there were no differences in monoamine content, monoamine biosynthesis and monoamines activity in the prefrontal cortex, hippocampus, hypothalamus and striatum in adulthood. These results indicate that long-lasting changes in social behavior following social stress during adolescence are not accompanied by changes in brain monoamine content, biosynthesis and turnover. [Copyright &y& Elsevier]

Abstract: Social stress is prevalent in many facets of modern society. Epidemiological data suggest that stress is linked to the development of overweight, obesity and metabolic disease. Although there are strong associations between the incidence of obesity with stress and elevated levels of hormones such as cortisol, there are limited animal models to allow investigation of the etiology of increased adiposity resulting from exposure to stress. Perhaps more importantly, an animal model that mirrors the consequences of stress in humans will provide a vehicle to develop rational clinical therapy to treat or prevent adverse outcomes from exposure to chronic social stress. In the visible burrow system (VBS) model of chronic social stress mixed gender colonies are housed for 2 week periods during which male rats of the colony quickly develop a dominance hierarchy. We found that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity that occurs, in part, through neuroendocrine alterations and changes in food intake amount. Although subordinate rats are hyperphagic following social stress they do not increase their intake of sucrose solution as control and dominants do suggesting that they are anhedonic. Consumption of a high fat diet does not appear to affect development of a social hierarchy and appears to enhance the effect that chronic stress has on body composition. The visible burrow system (VBS) model of social stress may be a potential laboratory model for studying stress-associated metabolic disease, including the metabolic syndrome. [Copyright &y& Elsevier]

Abstract: At the onset of agonistic social challenge, individuals must assess the degree of threat the opponent represents in order to react appropriately. We aimed to characterize the neuroendocrine changes accompanying this period of initial social assessment using the lizard Anolis carolinensis. Conveyance of aggressive intent by male A. carolinensis is facilitated by rapid postorbital skin darkening (eyespot), whereas eyespot presence inhibits opponent aggression. By manipulating this visual signal, we also investigated whether differing neuroendocrine changes were evoked by initial presentation of varying levels of social threat. Subjects were painted postorbitally either with black paint (high threat level), green paint (low threat level) or water (controls). Painted animals were presented with a mirror and sampled immediately upon exhibiting aggressive intent towards the reflected simulated opponent, but before producing behaviors such as motor pattern-based displays. Control animals (blank surface presented) were sampled at times derived from averaging response times of painted subjects. Brains and plasma were analyzed for monoamine activity and catecholamine levels using electrochemical HPLC. Social threat evoked increases in plasma catecholamine levels indistinguishable from those caused by brief environmental disturbance. However, brief social challenge caused distinct rapid increases in amygdala and nucleus accumbens (NAc) dopamine and serotonin levels. Amygdalar changes were associated with general social threat presence, but NAc monoamines were affected by both threat level and subject motivation to engage in confrontation. This suggests that specific rapid activity changes in key forebrain limbic nuclei differ according to the degree of social threat perceived at the start of the interaction. [Copyright &y& Elsevier]

Abstract: The individual food-demand behavior of juvenile European sea bass (Dicentrarchus labrax, L.) reared in groups under self-feeding conditions was investigated. The triggering activity on self-feeder, i.e. index of the food-demand activity, agonistic interactions and territorial behavior were monitored for periods of 42 to 68 days in six groups of 50 fish. The specific growth rate was calculated and the brain serotonergic activity was used as a stable index of social stress. Inter-individual differences appeared in triggering activity and three groups were distinguished: 3–5 high-triggering fish, 17–30 low-triggering fish and the remaining individuals were null-triggering fish. There were no significant differences in specific growth rates calculated at the end of the experiment (day 42 or day 68) between individuals with high, low, and null food-demand (ANOVA, p >0.05). No territorial or agonistic behaviors were observed, however, there were significant differences in brain serotonergic activity between the three triggering groups (ANOVA, p =0.050 in telencephalon and p =0.004 in cerebellum). Specifically, high-triggering fish had lower serotonergic turnover than low or null-triggering fish. We put forth the hypothesis that fish with low or null-triggering activity could be stressed by the high activity of high-triggering individuals. [Copyright &y& Elsevier]

Abstract: The human population has slowly transformed from the “hunter–gatherer” period to the current environment of high energy consumption, minimal physical activity and a lifestyle that includes stress and anxiety. Modeling the current environment in the laboratory can help to elucidate mechanisms responsible for the development of obesity, diabetes and, ultimately, the metabolic syndrome. Using the visible burrow system (VBS) model of social stress we have begun to examine the short- and long-term consequences of chronic social stress on energy homeostasis. We demonstrated that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity and have additionally determined that this occurs, in part, through changes in food intake amount and behavior. Changes in body weight and body composition are similar or greater when animals are maintained on a high fat diet. These data suggest that consumption of a high-fat diet during social stress in the VBS, while it does not appear to affect development of a social hierarchy, enhances the effect that chronic stress has on body composition and may be more representative of what happens in humans in modern society where the typical diet has progressively moved toward higher calorie, high-fat foods. [Copyright &y& Elsevier]

Abstract: In many species, social-defeat stress induces behavioral changes in subordinate individuals. The present study examined how social-defeat stress affected scent-marking and approach behaviors in male Mongolian gerbils and whether socially defeated males selectively avoided dominant males. In Experiment 1, each of 11 gerbils was defeated by a dominant gerbil during a short social confrontation (10 min in total). For Experiment 2, the same animals were used two weeks after the end of Experiment 1. Each subject was again similarly defeated, but the two gerbils were then kept in the same cage, separated by a wire mesh for 24 h. Behavioral changes in socially defeated males were observed after social defeat; both experiments were replicated three times. After acute social defeat in Experiment 1, male gerbils did not change their scent-marking activity and frequently approached the dominant males. In contrast, males decreased scent-marking activity and approach behavior toward dominant males in Experiment 2. The amount of time defeated males approached unfamiliar males was also reduced, suggesting that social-defeat stress reduces scent-marking motivation and conspecific approach behavior rather than inducing social avoidance toward a specific individual. These findings showed that the severity of social-defeat stress is an important factor in subsequent behavioral changes in male Mongolian gerbils. [Copyright &y& Elsevier]

Abstract: The role of pair housing in the modulation of anxiety-like behaviour in socially and physiologically stressed mice was investigated. The protocol of psychosocial stress consisted of submitting male adult mice to daily social confrontation with a male conspecific for a period of thirteen days. In an attempt to study a possible effect of pair housing as a social support, each male mouse was housed with a female throughout the period of experimentation, except during the agonistic interactions. As a physiological stressor, 109 sheep red blood cells (SRBC)/ml were injected intraperitoneally on the 1st and 7th days of the experiments. The respective control groups were as follows: non-socially stressed, non-pair housed and saline-injected mice. The humoral immune response was analysed by haemagglutination assay. The level of anxiety-like behaviours was measured in the elevated plus-maze test on the 13th day of the experiment. As a result, no significant changes in humoral immunity to SRBC were observed in mice subjected to social confrontation in a neutral arena as compared to non-socially stressed mice. As a consequence, no effect of pair housing on humoral immunity to SRBC could be evaluated. Concerning the effects of pair housing on the anxiety-like behaviours, it was possible to demonstrate that the pair housing proved to be effective in modulating anxiety-like behaviour, although in the stressed groups the percentage of time in the open arms and the time in risk assessment did not change in a symmetrical opposite form, as expected. The physiological stressor induced an anxiety-like behaviour that was not reversed by the pair housed condition. This suggests that different types of stressors activate different neural and peripheral pathways, which may or may not be modulated by pair housing, a finding that deserves our attention as a way to better understand the mechanisms that influence adaptations to stress. [Copyright &y& Elsevier]

Abstract: A single social defeat by a dominant conspecific induces long-term changes in several physiological and behavioral parameters in rats. These changes may represent an increased vulnerability to subsequent stress and stress-related pathology. Environmental factors, in particular possibilities for social interactions, could modulate these effects. Therefore, we assessed the influence of social environment on susceptibility for the long-term effects of social defeat. Socially housed males of an unselected strain of wild-type rats were equipped with radio-telemetry transmitters that recorded heart rate, temperature and activity. They were individually subjected to defeat and subsequently either housed alone or returned to their group. Behavioral and physiological responses to various novelty stressors were determined during a three-week period after the social defeat. Furthermore, changes in baseline behavior and physiology following defeat were studied in the rat''s homecage. The results show a complex interaction between defeat and housing conditions. Depending on the parameters measured, effects were caused by both isolation alone, defeat alone or a combination of both defeat and isolation. Individual housing alone caused a characteristic hyperactive response to novelty stress. Though defeat did not affect behavioral responses, it amplified the physiological response to novelty and social housing did not attenuate this effect. However, social housing did reduce the effects of defeat on heart rate, temperature and activity in the home cage and completely prevented defeat-induced weight loss. Together these results indicate that social housing may indeed positively affect the animal''s capacity to cope with stressors. [Copyright &y& Elsevier]

Abstract: Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing potential of a single exposure to stress is not clear. Both drug- and stress-induced sensitization depend on an enhanced dopaminergic neurotransmission in the mesolimbic DA system. Apart from responding to rewards, this system is also involved in responding towards aversive social stimuli. Therefore, social stressors may be particularly effective in inducing cross-sensitization to stimulant drugs. We examined the time course of sensitization to the locomotor effects of the stimulant, AMPH, following a single social stressor: a social defeat. Wistar rats were exposed in a resident–intruder paradigm to an unfamiliar dominant male conspecific (Wild-Type Groningen), resulting in defeat. The locomotor effects of a subsequent AMPH challenge (0.25 or 1.0 mg/kg) were evaluated 3, 14, and 21 days later by scoring horizontal movement in an open field. AMPH had significantly larger locomotor-activating effects in animals that had been defeated 3 days earlier compared to nondefeated controls. However, this sensitized response was no longer present 14 or 21 days after defeat. Therefore, we conclude that social defeat induces short-lasting cross-sensitization to the locomotor effects of AMPH in rats, but is not sufficient for long-term sensitization. The transient enhancement of responses to dopaminergic drugs may be indicative of a temporary role of dopamine in the cascade of physiological and behavioral changes following social defeat. [Copyright &y& Elsevier]

Mongolian gerbils are a species of rodent in Asia living in families, although aggression occurs within these social units. The aim of this study was to determine the causes for the surge of intrafamily aggression and to characterize different types of animals. Due to behavioral measures, animals were assigned to distinct social categories and the consequences of social stress were analyzed on an individual level. Four families established from founder pairs were kept for up to 2.5 years in large enclosures. Social interactions within each family were recorded for at least 5 days per week throughout the long-term experiment and fecal samples were collected weekly for the determination of corticosterone concentration. Moreover, adrenals were weighed and histologically analyzed. Two main causes for the outbreak of aggression were distinguished: changes in family structure and female competition for reproduction. As a result of these aggression periods, it was possible to divide animals into social categories: (1) integrated family members (IFM), (2) founder pair animals (FPA) and (3) expelled family members (EFM). Integrated animals had the lightest adrenal glands [related to the fat-free mass (FFM)] and lowest corticosterone level in aggression periods. Founder animals were never attacked by other members, reproduced successfully and displayed the highest stress level in most of the measured parameters. EFM were attacked and excluded mainly by the founder females. Their stress level was intermediate. [Copyright &y& Elsevier]

The visible burrow system (VBS) is an ethologically relevant model of social stress, which has been used to study the aggression of male rats in a social context. Previous studies using the VBS have established physiological, endocrine, and neurochemical characteristics associated with chronic social stress in dominant and subordinate animals. A critical criterion in establishing an animal model for research is the replication of findings and the independent validation of the model. Here, we independently confirm previously reported findings and include novel control groups that are important in dissociating the effects of chronic social stress from those resulting from group-housing the male rats in an “enriched environment”. Furthermore, we show that whereas the VBS model is useful for males, it is not effective for studies of females because they do not form dominance hierarchies when housed in groups. We also extend the use of the VBS model to examine the etiology of stress-induced anorexia and obesity, finding that weight loss in subordinate rats is attributable to decreased adipose and lean tissue, whereas in dominant rats, it is associated only with adipose tissue loss. Consistent with this, the adiposity hormones leptin and insulin are decreased in subordinates and, to a lesser extent, in dominants, compared with the controls. In summary, the VBS model of chronic social stress is an ethologically relevant animal model and provides a valuable tool for studies of stress-related conditions and pathologies. [Copyright &y& Elsevier]