Effects Of Chronic Social Stress Research Articles

Behavioral phenotype of C57Bl/6 mice that endured bullying during infant age period

BACKGROUND: According to UNESCO data for 2018, every third student is involved in bullying. To study the impact of social conflicts on the state of the nervous system the K. Michek model of chronic social stress was used, but the study of the effects of chronic social stress on prepubertal animals has not been conducted. AIM: To analyze the effect of chronic stress in infant age period to the behavioral phenotype of C57Bl/6 mice in early and long-term periods. MATERIALS AND METHODS: The objects of the study were male C57Bl/6 mice (n=48). For bullying modeling we chose chronic social stress in infant age period from 20 to 29 postnatal day (P20–P29) according to the “resident–intruder” scheme. Mice were divided into two subgroups to study the early (P31–P35, infant age period) and long-term (P57–P74, adulthood) consequences of chronic social stress. For the behavioral phenotyping we used the following tests: “open field” test, three-chamber social test, object recognition test, passive avoidance task and Barnes maze. RESULTS: Bullying modeling led to the changes in the behavioral phenotype both in infant age and in adulthood. The behavioral phenotype in infant age period was characterized by increased social activity and recognition, high anxiety, decreased locomotor and exploratory activity, impaired recognition of inanimate objects, but good characteristics of learning, working and long-term memory. In adulthood, the behavioral phenotype of mice retained high anxiety, low level of exploratory activity, good learning and memory characteristics, decline in social recognition in three-chamber test, while the recognition of inanimate objects was preserved at the same level. CONCLUSION: Chronic social stress in infant age in a mouse model of bullying causes disruption of the behavioral phenotype in infant and adult age. Features of the behavioral phenotype of mice after bullying were an increase in anxiety and social isolation against the background of the ability to learn and good memory.

Exploring transcriptional and post-transcriptional epigenetic regulation of crf and 11βhsd2 in rainbow trout brain during chronic social stress

Using dominance hierarchies in juvenile rainbow trout (Oncorhynchus mykiss) as a model of chronic social stress in fish, we explored whether epigenetic transcriptional and post-transcriptional mechanisms are involved in the gene expression of corticotropin-releasing factor (crf) and 11β-hydroxysteroid dehydrogenase (11βhsd2), key factors involved in the regulation of the endocrine stress axis response. In juvenile rainbow trout pairs, subordinate individuals display sustained elevation of circulating cortisol concentrations. Cortisol production is controlled by the hypothalamic-pituitary-interrenal (HPI) axis in fish and initiated by CRF release from the preoptic area (POA). Given that crf is modulated during chronic social stress, and that such stress has been implicated in the epigenetic regulation of crf in other taxa, we probed a role for epigenetic regulation of crf transcript abundance in chronically stressed rainbow trout. We also investigated the regulation of the cortisol-metabolising enzyme 11βhsd2 in the POA, which is upregulated in subordinates. The potential involvement of DNA methylation and microRNAs (miRNAs) in the regulation of crf transcript abundance was investigated during social stress in the POA of fish, as was the potential involvement of miRNAs in 11βhsd2 regulation. Although transcript abundances of crf were elevated in subordinate fish after 4 days, DNA methylation profiles within putative promoter sequences upstream of the crf gene were not significantly affected by chronic stress. An inverse relationship between crf and its predicted posttranscriptional regulator miR-103a-3p in the POA suggests that miRNAs may be involved in mediating the effects of chronic social stress on key components of the endocrine stress axis.

Effects of chronic social stress on oligodendrocyte proliferation-maturation and myelin status in prefrontal cortex and amygdala in adult mice

Stress-related neuropsychiatric disorders present with excessive processing of aversive stimuli. Whilst underlying pathophysiology remains poorly understood, within- and between-regional changes in oligodendrocyte (OL)-myelination status in anterior cingulate cortex and amygdala (ACC-AMY network) could be important. In adult mice, a 15-day chronic social stress (CSS) protocol leads to increased aversion responsiveness, accompanied by increased resting-state functional connectivity between, and reduced oligodendrocyte- and myelin-related transcript expression within, medial prefrontal cortex and amygdala (mPFC-AMY network), the analog of the human ACC-AMY network. In the current study, young-adult male C57BL/6 mice underwent CSS or control handling (CON). To assess OL proliferation-maturation, mice received 5-ethynyl-2′-deoxyuridine via drinking water across CSS/CON and brains were collected on day 16 or 31. In mPFC, CSS decreased the density of proliferative OL precursor cells (OPCs) at days 16 and 31. CSS increased mPFC myelin basic protein (MBP) integrated density at day 31, as well as increasing myelin thickness as determined using transmission electron microscopy, at day 16. In AMY, CSS increased the densities of total CC1+ OLs (day 31) and CC1+/ASPA+ OLs (days 16 and 31), whilst decreasing the density of proliferative OPCs at days 16 and 31. CSS was without effect on AMY MBP content and myelin thickness, at days 16 and 31. Therefore, CSS impacts on the OL lineage in mPFC and AMY and to an extent that, in mPFC at least, leads to increased myelination. This increased myelination could contribute to the excessive aversion learning and memory that occur in CSS mice and, indeed, human stress-related neuropsychiatric disorders.

Region- and receptor-specific effects of chronic social stress on the central serotonergic system in mice.

Serotonin (5-HT), via its receptors expressed in discrete brain regions, modulates aversion and reward processing and is implicated in various psychiatric disorders including depression. Stressful experiences affect central serotonergic activity and act as a risk factor for depression; this can be modelled preclinically. In adult male C57BL/6J mice, 15-day chronic social stress (CSS) leads to depression-relevant behavioural states, including increased aversion and reduced reward sensitivity. Based on this evidence, here we investigated CSS effects on 5-HT1A, 5-HT2A, and 5-HT2C receptor binding in discrete brain regions using in vitro quantitative autoradiography with selective radioligands. In addition, mRNA expression of Htr1a, 2a, 2c and Slc6a4 (5-HT transporter) was measured by quantitative PCR. Relative to controls, the following effects were observed in CSS mice: 5-HT1A receptor binding was markedly increased in the dorsal raphe nucleus (136%); Htr1a mRNA expression was increased in raphe nuclei (19%), medial prefrontal cortex (35%), and hypothalamic para- and periventricular nuclei (21%) and ventral medial nucleus (38%). 5-HT2A receptor binding was decreased in the amygdala (48%) and ventral tegmental area (60%); Htr2a mRNA expression was increased in the baso-lateral amygdala (116%). 5-HT2C receptor binding was decreased in the dorsal raphe nucleus (42%). Slc6a4 mRNA expression was increased in the raphe (59%). The present findings add to the translational evidence that chronic social stress impacts on the central serotonergic system in a region- and receptor-specific manner, and that this altered state of the serotonergic system contributes to stress-induced dysfunctions in emotional processing.

Evidence for decreased parasympathetic response to a novel peer interaction in older children with autism spectrum disorder: a case-control study

BackgroundIndividuals with autism spectrum disorder (ASD) often experience elevated stress during social interactions and may have difficulty forming and maintaining peer relationships. The autonomic nervous system (ANS) directs physiological changes in the body in response to a number of environmental stimuli, including social encounters. Evidence suggests the flexibility of the ANS response is an important driving factor in shaping social behavior. For youth with ASD, increased stress response and/or atypical ANS regulation to benign social encounters may therefore influence social behaviors, and, along with developmental and experiential factors, shape psychological outcomes.MethodsThe current study measured ANS response to a peer-based social interaction paradigm in 50 typically developing (TD) children and 50 children with ASD (ages 10–13). Respiratory sinus arrhythmia (RSA), a cardiac measure of parasympathetic influence on the heart, and pre-ejection period (PEP), a sympathetic indicator, were collected. Participants engaged in a friendly, face-to-face conversation with a novel, same-aged peer, and physiological data were collected continuously before and during the interaction. Participants also reported on state anxiety following the interaction, while parents reported on the child’s social functioning and number of social difficulties.ResultsLinear mixed models revealed that, while there were no diagnostic effects for RSA or PEP, older youth with ASD appeared to demonstrate a blunted parasympathetic (RSA) response. Further, increased severity of parent-reported social symptoms was associated with lower RSA. Youth with ASD reported more anxiety following the interaction; however, symptoms were not related to RSA or PEP response based on linear mixed modeling.ConclusionsPhysiological regulation, age, and social functioning likely influence stress responses to peer interactions for youth with ASD. Parasympathetic functioning, as opposed to sympathetic arousal, may be especially important in behavioral regulation, as older youth with ASD demonstrated atypical regulation and response to the social interaction paradigm. Future studies should help to further elucidate the developmental factors contributing to stress responses in ASD, the impact of physiological response on observable social behavior, and potential long-term consequences of chronic social stress in youth with ASD.

Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice

Introduction: Chronic stress causes a variety of physiological and behavioral alterations, including social impairments, altered endocrine function, and an increased risk for psychiatric disorders. Thereby, social stress is one of the most effective stressful stimuli among mammals and considered to be one of the major risk factors for the onset and progression of neuropsychiatric diseases. For analyzing the effects of social stress in mice, the resident/intruder paradigm of social defeat is a widely used model. Although the chronic social defeat stress model has been extensively studied, little is known about the effects of repeated or chronic social defeat stress on the endocannabinoid system (ECS). The present study aimed to understand the effects of chronic social stress on anxiety behavior and the levels of endocannabinoids (ECs) and two N-acylethanolamines (NAEs) in different brain regions of mice. Materials and Methods: Two-month-old, male C57Bl/6J mice were exposed to chronic psychosocial stress for 3 weeks. The effects of stress on anxiety behavior were measured using the light-dark box and hole board test. The EC levels of 2-arachidonoyl glycerol (2-AG) and anandamide (N-arachidonoylethanolamine [AEA]), as well as the levels of two NAEs (oleoylethanolamide [OEA] and palmitoylethanolamide), were analyzed by liquid chromatography-tandem mass spectrometry in the hippocampus, cerebellum, and cortex. Results: In comparison with control mice (n=12), mice exposed to social defeat stress (n=11) showed increased anxiety behaviors in the light-dark box and hole board test and gained significantly more weight during the experimental period. Additionally, chronic social stress induced differential alterations in the brain levels of 2-AG and AEA. More precisely, 2-AG levels were higher in the cortex and cerebellum, whereas reduced AEA levels were found in the hippocampus. Furthermore, we observed lower OEA levels in the hippocampus. Conclusion: The current study confirms that the ECS plays an essential role in stress responses, whereby its modulation seems to be brain region dependent.

Impact of Stress on Gamma Oscillations in the Rat Nucleus Accumbens During Spontaneous Social Interaction.

Alteration in social behavior is one of the most debilitating symptoms of major depression, a stress related mental illness. Social behavior is modulated by the reward system, and gamma oscillations in the nucleus accumbens (NAc) seem to be associated with reward processing. In this scenario, the role of gamma oscillations in depression remains unknown. We hypothesized that gamma oscillations in the rat NAc are sensitive to the effects of social distress. One group of male Sprague-Dawley rats were exposed to chronic social defeat stress (CSDS) while the other group was left undisturbed (control group). Afterward, a microelectrode array was implanted in the NAc of all animals. Local field potential (LFP) activity was acquired using a wireless recording system. Each implanted rat was placed in an open field chamber for a non-social interaction condition, followed by introducing another unfamiliar rat, creating a social interaction condition, where the implanted rat interacted freely and continuously with the unfamiliar conspecific in a natural-like manner (see Supplementary Videos). We found that the high-gamma band power in the NAc of non-stressed rats was higher during the social interaction compared to a non-social interaction condition. Conversely, we did not find significant differences at this level in the stressed rats when comparing the social interaction- and non-social interaction condition. These findings suggest that high-gamma oscillations in the NAc are involved in social behavior. Furthermore, alterations at this level could be an electrophysiological signature of the effect of chronic social stress on reward processing.

Chronic Social Stress Leads to Reduced Gustatory Reward Salience and Effort Valuation in Mice.

Pathology of reward processing is a major clinical feature of stress-related neuropsychiatric disorders including depression. Several dimensions of reward processing can be impacted, including reward valuation/salience, learning, expectancy and effort valuation. To establish the causal relationships between stress, brain changes, and reward processing pathologies, valid animal models are essential. Here, we present mouse experiments investigating behavioral effects of chronic social stress (CSS) in association learning tests of gustatory reward salience and effort valuation. The reward salience test (RST) comprised Pavlovian pairing of a tone with gustatory reward. The effort valuation test (EVT) comprised operant responding for gustatory reinforcement on a progressive ratio schedule (PRS). All testing was conducted with mice at 100% baseline body weight (BBW). In one experiment, mice underwent 15-day CSS or control handling (CON) and testing was conducted using sucrose pellets. In the RST on days 16–17, CSS mice made fewer feeder responses and had a longer tone response latency, than CON mice. In a shallow EVT on days 19–20, CSS mice attained a lower final ratio than CON mice. In a second CSS experiment, mice underwent CSS or CON and testing was conducted with chocolate pellets and in the presence of standard diet (low effort/low reward). In the RST on days 16–18, CSS mice made fewer feeder responses and had a longer tone response latency, than CON mice. In a steep EVT on days 19–20, CSS and CON mice attained less pellets than in the RST, and CSS mice attained a lower final ratio than CON mice. At day 21, blood levels of glucose and the satiety adipokine leptin were similar in CSS and CON mice. Therefore, CSS leads to consistent reductions in reward salience and effort valuation in tests based on association learning. These reward pathology models are being applied to identify the underlying neurobiology and putative molecular targets for therapeutic pharmacology.

Oligodendrocyte gene expression is reduced by and influences effects of chronic social stress in mice.

Oligodendrocyte gene expression is downregulated in stress-related neuropsychiatric disorders, including depression. In mice, chronic social stress (CSS) leads to depression-relevant changes in brain and emotional behavior, and the present study shows the involvement of oligodendrocytes in this model. In C57BL/6 (BL/6) mice, RNA-sequencing (RNA-Seq) was conducted with prefrontal cortex, amygdala and hippocampus from CSS and controls; a gene enrichment database for neurons, astrocytes and oligodendrocytes was used to identify cell origin of deregulated genes, and cell deconvolution was applied. To assess the potential causal contribution of reduced oligodendrocyte gene expression to CSS effects, mice heterozygous for the oligodendrocyte gene cyclic nucleotide phosphodiesterase (Cnp1) on a BL/6 background were studied; a 2 genotype (wildtype, Cnp1+/- ) × 2 environment (control, CSS) design was used to investigate effects on emotional behavior and amygdala microglia. In BL/6 mice, in prefrontal cortex and amygdala tissue comprising gray and white matter, CSS downregulated expression of multiple oligodendroycte genes encoding myelin and myelin-axon-integrity proteins, and cell deconvolution identified a lower proportion of oligodendrocytes in amygdala. Quantification of oligodendrocyte proteins in amygdala gray matter did not yield evidence for reduced translation, suggesting that CSS impacts primarily on white matter oligodendrocytes or the myelin transcriptome. In Cnp1 mice, social interaction was reduced by CSS in Cnp1+/- mice specifically; using ionized calcium-binding adaptor molecule 1 (IBA1) expression, microglia activity was increased additively by Cnp1+/- and CSS in amygdala gray and white matter. This study provides back-translational evidence that oligodendrocyte changes are relevant to the pathophysiology and potentially the treatment of stress-related neuropsychiatric disorders.

Delta Opioid Receptor Signaling Promotes Resilience to Stress Under the Repeated Social Defeat Paradigm in Mice.

The adaptation to chronic stress is highly variable across individuals. Resilience to stress is a complex process recruiting various brain regions and neurotransmitter systems. The aim of this study was to investigate the involvement of endogenous opioid enkephalin (ENK) signaling in the development of stress resilience in mice. The translational model of repeated social defeat (RSD) stress was selected to mimic the unpredictable disruptions of daily life and induce resilience or vulnerability to stress. As in humans, adult C57BL/6J mice demonstrated a great variability in their response to stress under this paradigm. A social interaction (SI) test was used to discriminate between the phenotypes of resilience or vulnerability to stress. After social defeat, the expression levels of ENK mRNA and their delta opioid receptors (DOPr) were quantified in the basolateral amygdala (BLA) and BLA-target areas by in situ hybridization. In this manner, ENK mRNA levels were found to decrease in the BLA and those of DOPr in the ventral hippocampus (HPC) CA1 of vulnerable mice only. Stimulating the DOPr pathway during social defeat by pharmacological treatment with the nonpeptide, selective DOPr agonist SNC80 further induced a resilient phenotype in a majority of stressed animals, with the proportion of resilient ones increasing from 33% to 58% of the total population. Ultrastructural analyses additionally revealed a reduction of oxidative stress markers in the pyramidal cells and interneurons of the ventral HPC CA1 upon SNC80 treatment, thus proposing a mechanism by which ENK-DOPr signaling may prevent the deleterious effects of chronic social stress.

Social stress-induced blood pressure increase in borderline hypertensive rats is associated with endothelial dysfunction in the resistant arteries

ObjectivesSeveral studies have observed that altered endothelial function is involved in the development of stress-induced hypertension. The aim of this study was to investigate the effects of chronic social stress (crowding) on endothelium-dependent relaxation (EDR) of the superior mesenteric artery (SMA) and of small resistant mesenteric arteries (MA) as well as on neurogenic contractions of SMA in adult borderline hypertensive rats (BHR).MethodsTwelve-week-old BHR (offspring of spontaneously hypertensive dams and Wistar-Kyoto sires) males were exposed to crowding (living space: 200 cm2/rat) for eight weeks. Control BHR were kept in the groups of four rats per cage (living space: 480 cm2/rat). Systolic blood pressure (sBP) was determined by the tail-cuff method.Vascular function was investigated in the isolated arteries at isometric conditions.EDR was assessed using acetylcholine test.ResultsCrowding significantly increased sBP of BHR to the hypertensive values. Results showed that stress did not affect total acetylcholine-induced relaxation and its nitric oxide (NO)-dependent and NO-independent components in the SMA. In the resistant MA, stress reduced total acetylcholine-induced relaxation by reducing NO-independent component, without the alterations of its NO-dependent component.However, stress failed to affect significantly neurogenic contractions of SMA elicited by electrical stimulation of perivascular sympathetic nerves and vasoconstriction induced by exogenous noradrenaline in SMA.ConclusionIn conclusion, chronic social stress can accelerate the development of hypertension in BHR, which seems to be associated with NO-independent endothelial dysfunction in small resistant arteries.Supported by the grants VEGA No. 2/0190/17 and APVV-16-0263.

Effects of chronic social stress in both social interaction and expression of serotonin 5-HT1A receptors in the paraventricular and the supraoptic nuclei of the hypothalamus.

Effects of chronic social stress in both social interaction and expression of serotonin 5-HT1A receptors in the paraventricular and the supraoptic nuclei of the hypothalamus.

Intergenerational accumulation of impairments in maternal behavior following postnatal social stress

Early adversity such as depressed maternal care can have long-term physiological and behavioral effects on offspring and future generations. Exposure to chronic social stress (CSS), an ethologically model of postpartum depression and anxiety, during lactation impairs maternal care and exerts similar effects on the F1 dam offspring of the stressed F0 dams. These changes associate with increased corticosterone and neuroendocrine alterations. CSS F2 offspring further display decreased social behavior as juveniles and adults and decreased basal levels of corticosterone. This current study investigates the intergenerational inheritance of alterations in maternal behavior in F2 CSS dams together with neuroendocrine and immune markers to explore whether aspects of maternal behavior are intergenerationally inherited through immune and neuroendocrine mechanisms. We find that defects in maternal care behavior persist into the F2 generation with F2 dams exhibiting a pervasively depressed maternal care and increased restlessness throughout lactation. This occurs together with reduced basal cortisol (in contrast to an increase in F1 dams), a lack of changes in neuroendocrine gene expression, and reduced serum ICAM-1 (intercellular adhesion molecule-1) levels - a marker for inflammation and blood–brain barrier integrity. The data support the hypothesis that the effects of chronic social stress can accumulate across multiple generations to depress maternal care, increase restlessness and alter basal functioning of the immune system and hypothalamic pituitary adrenal axis.

Chronic social stress leads to altered sleep homeostasis in mice

Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1–4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression.

A closer look at the subordinate population within the visible burrow system

The visible burrow system (VBS) utilizes the natural social behavior of rodents to model chronic social stress. Classically, when male and female rats are housed together in the VBS a dominance hierarchy rapidly forms with one dominant (DOM) and three subordinate (SUB) males. SUB animals show signs of chronic social stress, including loss of body weight and elevated basal corticosterone. This study furthered examined differences among the SUB population. Quantitative observations across numerous VBS colonies within the Sakai Lab suggest that there is variability in the effects of stress on the SUB population, specifically that some animals may experience more severe effects of chronic social stress than others. To further examine this observation, SUB animals were classified as OMEGA if they received a disproportionate amount of their colonies' wounds. OMEGA animals received more wounds to their body compared to SUB (P<0.0001) and lost significantly more weight throughout the stress period compared to all other VBS-housed animals (group×time interaction P<0.0001). Following VBS housing it was determined the OMGEA also lost lean body mass (P<0.01 vs. controls and DOM), are hyporesponsive to an acute restraint challenge (P<0.01 vs all other groups) and show depressive-like behavior during a forced swim test. Furthermore, expression of neuropeptide Y within the amygdala, known for anxiolytic properties following chronic stress, was elevated among OMEGA (group×region interaction P<0.001). Together these observations suggest that an additional phenotype exists among the SUB animals within a VBS colony and represents the variability of the effects of chronic social stress.

Effects of Chronic Social Stress and Maternal Intranasal Oxytocin and Vasopressin on Offspring Interferon-γ and Behavior.

Recent studies support the hypothesis that the adverse effects of early-life adversity and transgenerational stress on neural plasticity and behavior are mediated by inflammation. The objective of the present study was to investigate the immune and behavioral programing effects of intranasal (IN) vasopressin (AVP) and oxytocin (OXT) treatment of chronic social stress (CSS)-exposed F1 dams on F2 juvenile female offspring. It was hypothesized that maternal AVP and OXT treatment would have preventative effects on social stress-induced deficits in offspring anxiety and social behavior and that these effects would be associated with changes in interferon-γ (IFNγ). Control and CSS-exposed F1 dams were administered IN saline, AVP, or OXT during lactation and the F2 juvenile female offspring were assessed for basal plasma IFNγ and perseverative, anxiety, and social behavior. CSS F2 female juvenile offspring had elevated IFNγ levels and exhibited increased repetitive/perseverative and anxiety behaviors and deficits in social behavior. These effects were modulated by AVP and OXT in a context- and behavior-dependent manner, with OXT exhibiting preventative effects on repetitive and anxiety behaviors and AVP possessing preventative effects on social behavior deficits and anxiety. Basal IFNγ levels were elevated in the F2 offspring of OXT-treated F1 dams, but IFNγ was not correlated with the behavioral effects. These results support the hypothesis that maternal AVP and OXT treatment have context- and behavior-specific effects on peripheral IFNγ levels and perseverative, anxiety, and social behaviors in the female offspring of early-life social stress-exposed dams. Both maternal AVP and OXT are effective at preventing social stress-induced increases in self-directed measures of anxiety, and AVP is particularly effective at preventing impairments in overall social contact. OXT is specifically effective at preventing repetitive/perseverative behaviors, yet is ineffective at preventing deficits in overall social behavior.

Effect of Chronic Social Stress on Endothelial Function of the Mesenteric Artery of Normotensive and Spontaneously Hypertensive Rats

Abstract The aim of the work was to study the effect of chronic social stress induced by increased population density, “crowding stress” on blood pressure and endothelial function of arteries of male normotensive Wistar and spontaneously hypertensive (SHR) rats. Based on the results, we assume that social stress-induced reduction in endothelium-dependent relaxation and increased blood pressure of SHR rats is most likely associated with decreased bioavailability of nitric oxide.

Chronic social subordination stress modulates glutamic acid decarboxylase (GAD) 67 mRNA expression in central stress circuits

Chronic social subordination is a well-known precipitant of numerous psychiatric and physiological health concerns. In this study, we examine the effects of chronic social stress in the visible burrow system (VBS) on the expression of glutamic acid decarboxylase (GAD) 67 and brain-derived neurotropic factor (BDNF) mRNA in forebrain stress circuitry. Male rats in the VBS system form a dominance hierarchy, whereby subordinate males exhibit neuroendocrine and physiological profiles characteristic of chronic exposure to stress. We found that social subordination decreases GAD67 mRNA in the peri-paraventricular nucleus region of the hypothalamus and the interfascicular nucleus of the bed nucleus of the stria terminalis (BNST), and increases in GAD67 mRNA in the hippocampus, medial prefrontal cortex, and dorsal medial hypothalamus. Expression of BDNF mRNA increased in the dorsal region of the BNST, but remained unchanged in all other regions examined. Results from this study indicate that social subordination is associated with several region-specific alterations in GAD67 mRNA expression in central stress circuits, whereas changes in the expression of BDNF mRNA are limited to the BNST.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence.

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence.

P.1.h.005 Extended effects of chronic social stress on the behaviors of adolescents in adulthood

P.1.h.005 Extended effects of chronic social stress on the behaviors of adolescents in adulthood