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PubMed2007

Effects of social isolation and restraint on adrenocortical responses and hypoalgesia in loose-housed dairy cows.

Effects of social isolation or restraint, applied outside the home pen, on adrenocortical and nociceptive responses were examined in 28 loose-housed dairy cows. Treatments lasted 15 min and consisted of social isolation in novel surroundings or restraint by the head in a test pen. A control treatment was applied in the test pen as well. Each cow was exposed to all treatments in a balanced order, with 3 to 4 d between treatments. Compared with the control treatment, social isolation in novel surroundings led to increased plasma concentration of cortisol (P < 0.001) as well as to indications of hypoalgesia [posttreatment lack of decrease in latency to respond toward nociceptive laser stimulation, a tendency for decreased frequency of kicking in the pauses between laser stimulations (P = 0.06), and an increased proportion of leg moving (least possible active response) after treatment (P = 0.04)]. Indications of hypoalgesia were also observed after restraint (reduced kicking in response to laser stimulation, P = 0.04); however, the indications were to a lesser extent than after social isolation, and restraint treatment did not lead to increased plasma concentration of cortisol. For control and restraint treatment, an initial increase (P < 0.02) in plasma concentration of cortisol was found, suggesting effects of pretreatment factors such as handling. No correlations between adrenocortical and nociceptive responses toward social isolation were found. The results confirm earlier reports stating that nociceptive changes induced by environmental challenges can be shown in dairy cows, even when they are kept in groups and removed from the home pen during the study of stress responses. However, testing outside the home pen seemed to affect the nociceptive and adrenocortical responses, thereby suggesting that care should be taken to avoid effects of pretreatment situational factors.

Animals↗

PubMedDate not supplied

[Effects of antidepressants in models of brain self-stimulation and place preference after prolong social isolation and alcoholization].

In rats rearing in social isolation since 17th day of life and treated with 5-15% ethanol solution within 3 months, the effects of antidepressants on self-stimulation of lateral hypothalamus and place preference were studied. The comparative study of seven antidepressants with different mechanism of action (fluoxetine, maprotiline, tianaptine, pyrazidol, sertraline, citalopram, mianserin) was shown that pyrazidol and tianeptine and in a less degree sertraline and citalopram possessed the significant antidepressant activity in the model of social isolation and maprotiline and tianeptine did in model of alcoholization. It is concluded that antidepressants studied activate the reinforcing properties of the brain, that is associated with the involvement of both the catecholamine and serotonin system, working reciprocally.

Animals↗

PubMed2003

Hyperactivity to novelty induced by social isolation is not correlated with changes in D2 receptor function and binding in striatum.

RATIONALE: Prolonged social isolation has been reported to induce different behavioral disturbances, among the most consistent of which are the increased locomotor response to novelty and the effects of psychostimulants. While these behavioral changes have been partly related to a dysregulation of dopaminergic activity in striatum (dorsal and ventral), the involvement of changes in the function of dopamine receptors is still a matter of controversy. OBJECTIVES: To investigate the effects of prolonged social isolation on the function of D2 receptors at both the behavioral and biochemical levels. METHODS: Sprague-Dawley rats were randomly placed at 21 days of age in groups or isolation for 2 months. Horizontal and vertical locomotor activities induced by novelty and also by systemic injections of the D2 agonist quinpirole (0.15, 0.50 and 1.5 mg/kg i.p.) and their modulation by the A2A agonist CGS 21680 (0.1 mg/kg i.p.) were studied. The effects of social isolation on the avoidance learning assessed by the passive avoidance test were also studied. Binding experiments were performed to study the number and affinity of D2 receptors by means of saturation and competition experiments with the D2 antagonist [(3)H]-raclopride and the interaction between D2 receptors and the G-protein by means of [(35)S]-GTPgammas binding in dorsal/ventral striatal membranes of both grouped and isolated rats. RESULTS: Rats reared in isolation were hyperactive to a novel environment and showed shorter retention latencies in the passive avoidance test. Isolation rearing did not modify the increase in motor activity produced by quinpirole nor the counteraction of these effects by the simultaneous stimulation of A2A receptors. Likewise, the number, affinity and functional efficacy of D2 receptors were not changed by social isolation. CONCLUSIONS: These results suggest that the hyperactivity to novelty and psychostimulants as well as other behavioral changes induced by social isolation do not parallel changes in the in vivo function or binding of D2 receptors in dorsal/ventral striatum.

Animals↗

PubMed2026

Post-weaning social isolation increases reward-seeking behavior in mice.

Social isolation is a growing public health concern. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of social isolation (SI) during adolescence (postnatal day 21-35) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (rCPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI improved performance in the rCPT and the improvement in performance was consistent across time bins within the 45-minute testing session. There were no effects of SI on reaction times or reward retrieval latencies. A possible confound for performance in the rCPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both PR and FR schedules of reinforcement and found that SI mice had higher breakpoints on a PR4 schedule and earned significantly more reinforcers on an FR1 schedule of reinforcement compared to their group-housed littermates, suggesting that high performance in the CPT may be due to increased motivation for food rewards. These data indicate that SI during adolescence has significant effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

Animals↗

PubMed2004

Social isolation stress significantly enhanced the disruption of prepulse inhibition in mice repeatedly treated with methamphetamine.

Repeated administration of methamphetamine (METH) causes reverse tolerance or behavioral sensitization in mice. However, the effects of social isolation stress on the METH-caused reverse tolerance have not been studied until now. The aim of this study was to investigate the effects of social isolation stress on METH-caused reverse tolerance by examining the prepulse inhibition of startle response (PPI). PPI was tested in socially isolated and grouped mice after repeated METH injections. Locomotor activity and PPI were also examined just after a four-week isolation rearing period as a control experiment. After completing behavioral experiments, the mice were sacrificed, and the contents of monoamines, including histamine in the brain, were measured. Social isolation stress significantly lowered the locomotion and disrupted PPI. Repeated injections of METH enhanced the effects of social isolation on PPI. The content of dopamine and histamine significantly increased in the cortex, and the turnover rate of dopamine decreased significantly. These findings demonstrate that social isolation stress significantly enhances METH-induced behavioral sensitization and that the altered histaminergic neuron system might play an important role in METH-induced behavioral sensitization in addition to dopaminergic and serotoninergic neurotransmission. Our data suggest that social isolation is involved in the development of METH-induced psychosis, schizophrenia, and other related psychiatric disorders.

Animals↗

PubMed2005

Social isolation and the inflammatory response: sex differences in the enduring effects of a prior stressor.

Numerous epidemiological studies have demonstrated an association between persistent social isolation and "all-cause" morbidity and mortality. To date, no causal mechanism for these findings has been established. Whereas animal studies have often reported short-term effects of social isolation on biological systems, the long-term effects of this adverse psychological state have been understudied. This is the first animal study to examine the effects of long-term social isolation from weaning through young adulthood on an innate inflammatory response linked to numerous disease processes. Results presented here offer a plausible link between vulnerability to disease and social neglect. For socially isolated male and female Sprague-Dawley rats, a naturally gregarious species, formation of a granuloma in response to a subcutaneous injection of carrageenin (seaweed) was significantly delayed compared with the response of animals housed in single-sex groups of five. Significant sex differences, however, emerged when an acute prior stressor was superimposed on the experience of chronic social isolation. In this context, isolated females produced a more robust inflammatory response than isolated males. This sexual dimorphism at the nexus of chronic social isolation, acute stress, and inflammatory processes may account for the observation in humans that men with low levels of social integration are more vulnerable to disease and death than women.

Animals↗

PubMed2005

Social isolation, support, and capital and nutritional risk in an older sample: ethnic and gender differences.

This study examines the relationships that exist between social isolation, support, and capital and nutritional risk in older black and white women and men. The paper reports on 1000 community-dwelling older adults aged 65 and older enrolled in the University of Alabama at Birmingham (UAB) Study of Aging, a longitudinal observational study of mobility among older black and white participants in the USA. Black women were at greatest nutritional risk; and black women and men were the groups most likely to be socially isolated and to possess the least amounts of social support and social capital. For all ethnic-gender groups, greater restriction in independent life-space (an indicator of social isolation) was associated with increased nutritional risk. For black women and white men, not having adequate transportation (also an indicator of social isolation) was associated with increased nutritional risk. Additionally, for black and white women and white men, lower income was associated with increased nutritional risk. For white women only, the perception of a low level of social support was associated with increased nutritional risk. For black men, not being married (an indicator of social support) and not attending religious services regularly, restricting activities for fear of being attacked, and perceived discrimination (indicators of social capital) were associated with increased nutritional risk. Black females had the greatest risk of poor nutritional health, however more indicators of social isolation, support, and capital were associated with nutritional risk for black men. Additionally, the indicators of social support and capital adversely affecting nutritional risk for black men differed from those associated with nutritional risk in other ethnic-gender groups. This research has implications for nutritional policies directed towards older adults.

Aged↗

PubMed1998

Neuroendocrine and immunocytochemical demonstrations of decreased hypothalamo-pituitary-adrenal axis responsiveness to restraint stress after long-term social isolation.

We have studied the effects of long-term social isolation of male Wistar rats, after early weaning (16 days), on the activity of the hypothalamo-pituitary-adrenal (HPA) axis. In addition to studying basal HPA activity, the response of the HPA axis to 15 min of immobilization stress was examined. Plasma corticosterone concentrations were measured, and the relative weights of adrenal glands, thymus, and testes were obtained, the latter to check whether gonadal function was affected by the isolation paradigm. Moreover, we carried out a quantitative immunohistochemical study of pituitary ACTH and its hypothalamic secretagogues: CRF, arginine vasopressin (AVP), and oxytocin (OT), both at the level of the synthesizing cell bodies in the hypothalamic paraventricular nucleus and of the releasing fibers in the median eminence (ME). Body weight and daily consumption of food and water were not altered, but social isolation caused a reduction in plasma corticosterone levels, both under basal and stress-stimulated conditions; this was correlated with an increased thymus weight, without affecting adrenal or testicular weights. The immunohistochemical study revealed that isolation caused a smaller increase in the number of ACTH-immunoreactive cells in the pars distalis of the anterior pituitary after exposure to restraint stress, as compared with control animals. This result indicates that fewer corticotrophs were activated by restraint stress in isolated animals, such cells being smaller and exhibiting a smaller ACTH-immunoreactive area than in control animals. Isolated animals also showed an increase in the content of CRF-ir fibers in the ME and a smaller decrease in the neuropeptide immunoreactivity after stress than that observed in control animals. This result could indicate a reduced release of CRF into the portal vasculature in response to acute stress and may partially explain the reduced activation of corticotrophs observed in the pituitary of isolated animals. However, no changes were found in the content of CRF, AVP, or OT within the paraventricular nucleus, nor of the AVP or OT content in the ME. The results of this study show that long-term social isolation after early weaning caused a hypofunction of the HPA axis in the adult rat. This hypofunction was particularly evident after exposure to an acute stressor, suggesting a desensitization of this axis to stressful stimuli.

Animals↗

PubMed2003

Neonatal social isolation alters both maternal and pup behaviors in rats.

The development of emotional behavior is dependent on the early experiences of the infant and the quality of maternal care. In these experiments, the effects of social isolation during the preweaning period on both pup behavior and maternal responsivity were examined. In the first study, the number of ultrasonic vocalizations (USVs) emitted after brief maternal separation was measured in neonatal rats with differing histories of social isolation. The social isolation procedure consisted of 5 days of daily separation from the dam and littermates for either 3 or 6 hr. At both ages tested, socially isolated pups vocalized significantly less than control pups. In the second study, the effects of prior isolation either daily for 5 previous days (Chronic Isolation) or for 4 hr prior to testing (Acute Isolation) were examined in a T-maze choice test. Pup vocalizations in the presence of the dam and dams' maternal behavior were assessed. When the dam was confined to the start box or during the maternal free access period, both Chronic and Acute Isolates vocalized less than pups that had never left the home nest. Dams spent more time with and licked and groomed more frequently and for a longer time both Chronic and Acute Isolates compared to pups that had always been with dams in the home nest. These results suggest that early isolation experience can alter subsequent responses to separation stress in neonatal rats and that maternal behavior is sensitive to the prior experiences of offspring.

Animals↗

PubMed2000

Morphine-induced sensitization of locomotor activity in mice: effect of social isolation on plasma corticosterone levels.

This study examined the influence of social isolation on behavioural sensitization to the locomotor effect of morphine and the link between this behaviour and plasma corticosterone concentrations. Four weeks isolation induced an increase in the locomotor effect of morphine. In social and isolated mice, repeated administrations (6) of morphine (one injection every 3 or 4 days) followed by 3 h in an actimeter induced behavioural sensitization to the locomotor effect of morphine. No interaction was observed between social isolation and behavioural sensitization to morphine. Resocializing previously isolated mice for 3 weeks reduced the morphine-induced locomotor effect without altering the behavioural sensitization. Corticosterone plasma levels were more increased (416%) in mice isolated 5 weeks than in mice isolated for 2 weeks (243%) and they return to the control levels following 3 weeks of resocialization. Since there was no interaction between the increase in morphine locomotor effect induced by social isolation and the morphine-induced behavioural sensitization, it is suggested that each of these two events acts independently. Whether or not a common mechanism (plasma corticosterone levels?) partly underlies both effects, the result resembles a simple additive effect.

Adrenal Cortex↗

PubMed2001

Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation.

Allopregnanolone (ALLO), is a brain endogenous neurosteroid that binds with high affinity to gamma-aminobutyric acid type A (GABA(A)) receptors and positively modulates the action of GABA at these receptors. Unlike ALLO, 5alpha-dihydroprogesterone (5alpha-DHP) binds with high affinity to intracellular progesterone receptors that regulate DNA transcription. To investigate the physiological roles of ALLO and 5alpha-DHP synthesized in brain, we have adopted a mouse model involving protracted social isolation. In the frontal cortex of mice, socially isolated for 6 weeks, both neurosteroids were decreased by approximately 50%. After administration of (17beta)-17-(bis-1-methyl amino carbonyl) androstane-3,5-diene-3-carboxylic acid (SKF105,111), an inhibitor of the enzyme (5alpha-reductase Type I and II) that converts progesterone into 5alpha-DHP, the ALLO and 5alpha-DHP content of frontal cortex of both group-housed and socially isolated mice decreased exponentially to 10%-20% of control values in about 30 min. The fractional rate constants (k h(-1)) of ALLO and 5alpha-DHP decline multiplied by the ALLO and 5alpha-DHP concentrations at any given steady-state estimate the rate of synthesis required to maintain that steady state. After 6 weeks of social isolation, ALLO and 5alpha-DHP biosynthesis rates were decreased to 30% of the values calculated in group-housed mice. Moreover, in socially isolated mice, the expression of 5alpha-reductase Type I mRNA and protein was approximately 50% lower than in group-housed mice whereas 3alpha-hydroxysteroid oxidoreductase mRNA expression was equal in the two groups. Protracted social isolation in mice may provide a model to investigate whether 5alpha-DHP by a genomic action, and ALLO by a nongenomic mechanism down-regulate the action of drugs acting as agonists, partial agonists, or positive allosteric modulators of the benzodiazepine recognition sites expressed by GABA(A) receptors.

Animals↗

PubMed2005

Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.

Animals↗

PubMed2001

Social isolation predicts re-hospitalization in a group of older American veterans enrolled in the UPBEAT Program. Unified Psychogeriatric Biopsychosocial Evaluation and Treatment.

OBJECTIVES: Does social isolation predict re-hospitalization in a group of older men enrolled in Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT), a mental health care-coordination project at nine Veterans Affairs Healthcare Centers nationwide? METHODS: The current study examined 123 UPBEAT patients located at West Los Angeles, whose ratings were available on the Lubben Social Network Scale (LSNS), the SF-36 scale, the Cumulative Illness Rating Scale (CIRS) and the Mental Health Index (MHI-38) Depression and Anxiety subscales. Within one year of enrollment, 55% of patients were re-hospitalized. Odds of re-hospitalization were calculated using two logistic regression models. Social isolation risk (LSNS) and demographic covariates were included. In addition, Model 1 contained depression and anxiety measures (MHI-38) and physician-rated medical burden (CIRS), while in Model 2, patient-perceived physical (PCS) and mental health (MCS) subscales from the SF-36 were included. RESULTS: The group of patients who were socially isolated or at high or moderate risk for isolation, were 4-5 times more likely to be re-hospitalized within the year, than low isolation risk patients. In both Models 1 (chi-square = 19.86; p = 0.031) and 2 (chi-square = 26.42; p = 0.002) demographic characteristics were not significant predictors of re-hospitalization, but social isolation risk was a significant predictor (Model 1: odds ratio (OR) = 5.31; 95% confidence intervals (CI) = 1.81-15.53; and Model 2: OR = 3.86; 95% CI = 1.39-10.73). In addition, MHI-Anxiety was a significant predictor (OR = 1.22; 95% CI = 1.05-1.43) in Model 1 and in Model 2, patient-perceived physical health significantly predicted re-hospitalization (OR = 0.91; 95% CI = 0.86-0.96). CONCLUSION: When controlling for other covariates, social isolation, physical health and mental health were significant risk factors for re-hospitalization. These findings underline the importance of assessing and addressing lack of social support, along with other factors, in the health care of older male veterans.

Aged↗

PubMed2006

Depressive symptoms, social isolation, and progression of coronary artery atherosclerosis: the Stockholm Female Coronary Angiography Study.

BACKGROUND: Although both depressive symptoms and social isolation in relation to coronary heart disease have been studied previously, few have examined their joint effects on coronary atherosclerosis progression in women. METHOD: Among the women enrolled in the Stockholm Female Coronary Angiography Study, Sweden, between 1991 and 1994, 102 were evaluated for coronary atherosclerosis progression using a computer-assisted standardized assessment, repeated quantitative coronary angiographic documentation, of the mean luminal diameter change over 3 years in 10 predefined coronary segments. Depressive symptoms and social isolation were assessed by standard questionnaires. RESULTS: Multivariable controlled mixed model ANOVAs revealed that women who were both depressed and socially isolated had the greatest disease progression: their absolute mean luminal diameter decreased by 0.18 mm [95% confidence interval (CI) = 0.11-0.24] and their percent narrowing was 5.5% (95% CI = 3.6-7.4), whereas in women who lacked both psychological risk factors, the mean luminal diameter decrease was 0.04 mm and their percent narrowing was 0.9%. These associations were independent of the baseline luminal diameter and standard risk factors, including age, smoking history, hypertension, and high-density lipoproteins. CONCLUSIONS: In women with coronary disease, depressive symptoms and social isolation in combination accelerated disease progression, suggesting a direct psychosocial effect on the atherosclerotic process. These findings provide an additional opportunity for therapeutic and preventive efforts against progression of coronary disease in women.

Adult↗

PubMed2000

Differential effects of social isolation upon body weight, food consumption, and responsiveness to novel and social environment in bombesin receptor subtype-3 (BRS-3) deficient mice.

The effects of social isolation on body weight gain, food consumption, and responsiveness to novel and social environment were assessed in an animal model for obesity, bombesin receptor subtype-3 (BRS-3) deficient mice. In Experiment 1, body weight gain and food consumption of group- and isolation-housed wild-type and BRS-3-deficient mice were compared. In wild-type mice, group-housed animals showed greater mean body weight gain and food consumption than did the isolation-housed cohort in the early stage of the experiment, whereas in BRS-3-deficient mice, the isolation-housed mice showed greater body weight gain and food consumption than the group-housed cohort by prolonged isolation housing. In Experiment 2, isolation-housed wild-type mice exhibited increased stereotypic and vertical movements relative to group-housed subjects in a novel environment, but this effect was not observed in BRS-3-deficient mice. In Experiment 3, when social response was assessed in animals housed in isolation, BRS-3-deficient mice exhibited lower social responses than did wild-type mice. We conclude that BRS-3-deficient mice and wild-type mice are differentially affected by social isolation. These results suggest that BRS-3 expression in the CNS may affect the neural mechanisms that regulate isolation effects in wild-type animals.

Aging↗

PubMed2000

Social isolation may influence responsiveness to infection with bovine herpesvirus 1 in veal calves.

An experiment was performed to develop a model to study the impact of stress on responsiveness to infection with bovine herpesvirus 1 (BHV1) in veal calves. Social isolation after previous group-housing was used as a putatively stressful treatment. Group-housed specific pathogen-free veal calves (n=8) were experimentally infected with BHV1 at the age of 12 weeks. Half of the calves were socially isolated at the time of infection. Clinical, virological and serological responses to BHV1, and adreno-cortical reactivity to exogenous ACTH were examined. In comparison with group-housed calves, calves socially isolated at the time of infection showed a diminished clinical and fever response, and delayed viral excretion after primary infection with BHV1. Four weeks after social isolation, basal cortisol levels before, and the integrated cortisol response after administration of a low dose of ACTH, were significantly depressed in socially isolated calves. The results suggest that social isolation in veal calves influences the response to an experimental BHV1 infection. A possible mechanism is discussed.

Adrenocorticotropic Hormone↗

PubMed1996

Social isolation in animal models of relevance to neuropsychiatric disorders.

Animal models of social isolation have been suggested to be relevant to several neuropsychiatric disorders; however, social isolation is usually not purely an alteration of social environment, as it often involves such factors as decreased complexity of the environment, loss of tactile stimulation, and increased metabolic demands of temperature maintenance. In this study, female prairie voles (Microtus ochrogaster, a highly social rodent) were assigned to four experimental groups: continued housing with sibs, with or without nesting material; and individual housing, with or without nesting material. Isolation increased serum corticosterone but did not alter weight. There was no statistical interaction between these two factors. In animal models, factors other than specifically social variables may contribute to the physiological response to social isolation, and the various aspects of the stress response may respond differentially to these factors.

Animals↗

PubMed1991

Impaired performance from brief social isolation of rhesus monkeys (Macaca mulatta): a multiple video-task assessment.

Social isolation has been demonstrated to produce profound and lasting psychological effects in young primates. In the present investigation, two adult rhesus monkeys (Macaca mulatta) were isolated from one another for up to 6 days and tested on 7 video tasks designed to assess psychomotor and cognitive functioning. Both the number and the quality (i.e., speed and accuracy) of responses were significantly compromised in the social isolation condition relative to levels in which the animals were tested together. It is argued that adult rhesus are susceptible to performance disruption by even relatively brief social isolation, and that these effects can best be assessed by a battery of complex and sensitive measures.

Animals↗