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Changes in cortical dendritic branching subsequent to partial social isolation in stumptailed monkeys.

Stumptailed monkeys were reared from 1 week after birth to 6 months of age in either a colony condition with the mother or in partial social isolation that allowed visual contact with the colony animals, but not physical contact. At 6 months of age the animals were killed and selected areas of the neocortex stained by the Golgi-Cox method. Relatively nonspiney cells of Layer IV were drawn and analyzed for complexity of dendritic branching. Isolation-reared animals had significantly decreased branching complexity in Motor I cortex when compared to the control animals. A transform of the data that related the number of branches to the number of previous branches showed a slight rearing effect in Somatosensory I cortex with the deprived animals having a lower rate of branching than the controls. We conclude that social isolation also includes a motoric deprivation that could account for these data.

Animals↗

Maternal separation and social isolation modulate the postnatal development of synaptic composition in the infralimbic cortex of Octodon degus.

We analysed the influence of preweaning periodic maternal separation followed by postweaning chronic social isolation on the development of synaptic composition in the infralimbic cortex of Octodon degus, a South American species formerly classified as a caviomorph rodent but now considered to belong to Lagomorpha (rabbits). Three groups of animals were analysed: (1) control pups which remained undisturbed with their families; (2) pups which were exposed to individual periodic maternal deprivation [postnatal day 1 (P1) until P21], followed by social isolation (P22 until P45); and (3) pups which were handled daily without being removed from the families (P1 until P21) and thereafter remained undisturbed with the family (P22 until P45). The mean synaptic density and mean projected height of synapses were quantified using the "dissector" method. In the deprived group, significantly higher (up to 137.8%) mean synaptic densities were found in layer II of the infralimbic cortex compared to normal control animals. In handled pups, asymmetric shaft synapses were significantly decreased (down to 54%) compared to the control group.These results indicate that early postnatal changes in the socio-emotional environment change the number of synaptic connections in the infralimbic cortex. Since this subregion of the medial prefrontal cortex is involved in a variety of emotional behaviors and plays a role in associative learning tasks, these environmentally induced synaptic changes may be indicative, and perhaps the cause, of alterations of behavioral and cognitive capacities.

Animals↗

The role of social isolation in the effects of alcohol on corticosterone and testosterone levels of alcohol-preferring and non-preferring rats.

AIMS: Alcohol has been reported to affect the hypothalamic-pituitary-gonadal axis (HPG-axis) and hypothalamic-pituitary-adrenal axis (HPA-axis) as expressed by increased or decreased corticosterone and testosterone levels. Both hormones have also been related to the aetiology of alcohol drinking and the development of alcoholism. Our aim has been to study these interrelations in animal models of alcohol drinking by using social isolation as a model of anxiety. METHODS: The effects of alcohol on serum testosterone and corticosterone concentrations were investigated in alcohol-preferring (AA) and alcohol non-preferring (ANA) rat lines. Animals were tested in mornings and afternoons with 0.75 and 1.5 g alcohol/kg. Half of the animals were kept in single cages, while the control animals were housed in groups of four individuals. RESULTS: The group-caged ANA rats displayed higher control corticosterone levels than the corresponding AA rats during morning sessions (P = 0.007). The AA rats displayed elevated corticosterone levels (AM: P = 0.047) and the ANA rats displayed reduced control corticosterone levels (PM: P = 0.016) in the single cage situation compared with the group-cage situation. Corticosterone concentrations were not affected by low doses and increased (P < 0.05) by high doses of alcohol in all test groups except for isolated AA rats during afternoon sessions. In general, more significant reductions in testosterone levels following alcohol administration were found in the ANA line. In group-caged AA rats, alcohol reduced testosterone levels, while no such effect was observed in isolated AA rats. CONCLUSIONS: We suggest that social isolation, representing stress, may constitute a situation in which the HPA and HPG axes are connected together in promoting alcohol drinking.

Animals↗

Incapacitation or death of a socially isolated parent or carer could result in the death of dependent children.

A study was undertaken to investigate features of infant and childhood fatalities that were a consequence of care by socially isolated adults suffering from significant medical conditions. Autopsy records at the Forensic Science Centre in Adelaide from July 1996 to June 2001 were searched for all cases where infants or children had died as a result of the incapacitation or death of an adult carer. A total of two cases were found, involving three children. The carers were aged 51 years (grandfather) and 20 years (mother) and had died at home from ischaemic heart disease and epilepsy, respectively. The children were all boys and were aged 1 year, 2.5 years and 3 years. The child victims had died of dehydration following the adult deaths. These cases demonstrate that infants and young children in the care of socially isolated and unwell adults could be at risk of significant injury or death if the carer dies or becomes incapacitated. The provision of medical-emergency buttons for such families, and/or the setting up of regular contact with medical clinics or neighbours are steps that could be taken to diminish the risk of such an outcome.

Adult↗

The effects of social isolation on the behavior of juvenile domestic cats.

The effects of social isolation on the behavior of juvenile domestic cats were assessed by rearing 4 male and 4 female infant kittens in each of the following rearing conditions: (1) mother-littermate; (2) mother-only; (3) brooder-littermate; and (4) brooder-only. They were then tested twice a week individually and twice a week socially from 2 to 6 1/2 months of age in a playroom, utilizing multiple categories of behavior. The mother-only-reared juveniles were hyperactive in both object play (when tested individually) and social play. The brooder-only-reared kittens displayed enhanced socially directed behavior and were generally hypergregarious, whereas the brooder-littermate-reared kittens displayed retarded social behavior. Observations indicated that littermate-deprived kittens did not learn social communication skills and that some prolonged separation effects existed for littermate-reared kittens. The results suggest that the determinants of social play are more complex than the determinants of object play.

Animals↗

Social isolation selectively reduces hippocampal brain-derived neurotrophic factor without altering plasma corticosterone.

It is well known that housing conditions may alter several physiological and behavioral parameters. In this study, we have investigated whether a prolonged period of partial social isolation can modify central brain-derived neurotrophic (BDNF) concentrations. Male Sprague-Dawley rats were singly housed for 8 weeks before hippocampi, prefrontal cortices and striata were collected for BDNF determination. Compared to rats housed two per cage, isolated rats showed a significant reduction on BDNF protein concentrations in the hippocampus while no changes were observed in the other brain regions examined. Moreover, housing condition had no effect on basal plasma corticosterone. On the basis of the proposed etiological participation of reduced central BDNF concentrations in affective disorders, our results would candidate social isolation as a model for the study of antidepressant treatments.

Animals↗

Social isolation increases the stimulatory effect of ethanol on locomotor activity.

The stimulatory effects of low alcohol doses are of great interest because of their role in human drinking and their possible relation to reinforcement from alcohol. The preferred animal model for studying them is the mouse. The effects of various doses of ethanol on locomotor activity were now studied in both group-housed mice and in mice socially isolated for 36-44 weeks. The housing situation was found to have a strong influence: a large stimulatory effect was observed in isolated mice but little effect was seen in group-housed animals. The results suggest that socially isolated mice are more sensitive to the stimulatory effect of ethanol on locomotor activity.

Animals↗

Early social isolation decreases the expression of calbindin D-28k in rat cerebellar Purkinje cells.

The main objective of this study was to analyze the effects of early social isolation on the expression of calbindin D-28k (CAD-28k) in cerebellar Purkinje cells. Sprague-Dawley rats were reared either in isolation (IC) or socially housed conditions (SC) from postnatal days 18-32. Half of the rats of each group were sacrificed at 32 days of age and the cerebella processed for immunocytochemical labeling against CAD-28k. The remaining IC animals were housed under standard conditions for re-socialization between postnatal days 32 and 62. The results indicate that Purkinje cells of rats reared under early isolation show a marked loss of CAD-28k immunoreactivity, and that this deficiency is recovered by later social interaction, although the thickness of the molecular layer remains reduced.

Animals↗

Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome.

Rearing rats in isolation has been shown to be a relevant paradigm for studying early life stress and understanding the genesis of depression and related affective disorders. Recent studies from our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibition of the acoustic startle, food hoarding and spontaneous locomotor activity. In addition, ex vivo neurochemical changes in the brains of isolated and grouped rats reared either in sawdust-lined or in grid-floor cages were determined by measuring dopamine and serotonin as well as their major metabolites in a "psychosis circuit" that includes mainly the hippocampus and selected hippocampal efferent pathways projecting towards the anterior cingulate and infralimbic cortices, nucleus accumbens, dorsolateral caudate nucleus, amygdala and entorhinal cortex. The results of the present study demonstrate that rearing rats in isolation (i) produces a syndrome of generalized locomotor hyperactivity; (ii) increases the startle response; (iii) impairs prepulse inhibition; (iv) tends to increase food hoarding behavior; (v) increases basal dopamine turnover in the amygdaloid complex; (vi) decreases basal dopamine turnover in the infralimbic part of the medial prefrontal cortex; and (vii) decreases basal turnover of serotonin in the nucleus accumbens. In the entorhinal cortex, dopamine neurotransmission seemed to be more sensitive to the caging conditions since a decreased basal turnover of dopamine was observed in grid-reared animals. Plasma corticosterone levels were also increased in grid-reared animals compared with rats reared in sawdust cages. Finally, isolates reared on grids showed a significant positive correlation between plasma corticosterone levels and dopamine in the left nucleus accumbens.Altogether, these results support the contention that there is a link between social isolation, attention deficit, spontaneous locomotor hyperactivity and reduced dopamine turnover in the medial prefrontal cortex. Furthermore, our data demonstrate that rearing rats in grid-floor cages represents a form of chronic mild stress associated with increased corticosterone levels, decreased basal turnover of entorhinal dopamine and increased dopamine activity in the left nucleus accumbens. Finally, a significant and selective decrease in the basal turnover of serotonin in the nucleus accumbens of isolated rats may be linked to the isolation-induced locomotor hyperactivity.

Acoustic Stimulation↗

Hypercortisolism associated with social subordinance or social isolation among wild baboons.

BACKGROUND: The phenomena of basal hypercortisolism and of dexamethasone resistance have long intrigued biological psychiatrists, and much is still unknown as to the causes and consequences of such adrenocortical hyperactivity in various neuropsychiatric disorders. We have analyzed basal cortisol concentrations and adrenocortical responsiveness to dexamethasone in a population of wild baboons living in a national park in Kenya. We tested whether social subordinance in a primate is associated with dexamethasone resistance. Furthermore, we examined whether individual differences in adrenocortical measurements were predicted by the extent of social affiliation in these animals. METHODS: Seventy yellow baboons (Papio cynocephalus) were anesthetized and injected with 5 mg of dexamethasone; the cortisol response was monitored for 6 hours. The animals were of both sexes in a range of ages and had known ranks in the dominance hierarchies within their troops. Extensive behavioral data were available for a subset of 12 adult males who were anesthetized under circumstances that also allowed for the determination of basal cortisol concentrations. RESULTS: The socially subordinate baboons were less responsive to dexamethasone than were the dominant ones; as one manifestation of this, postdexamethasone cortisol values were more than 3 times higher in the dozen lowest-ranking animals compared with the dozen highest. In addition, socially isolated males had elevated basal cortisol concentrations and showed a trend toward relative dexamethasone resistance. CONCLUSIONS: Our findings indicate that social status and degree of social affilitation can influence adrenocortical profiles; specifically, social subordinance or social isolation were associated in our study with hypercortisolism or feedback resistance.

Animals↗

[Domestication-related behavior as a factor for the long-term adaptation of the sheep hypothalamic-pituitary-adrenocortical system to social isolation].

The reaction of the hypothalamic-pituitary-adrenocortical axis (HPA) to social isolation from the herd was studied in 45 ewes of the Altaian breed at the age of 12, 16, and 27 months. The animals belonged to either "wild" or "domesticated" phenotypes which contrasted in the character of feeding and defensive responses to a human. The basal corticoid level in animals of both behavioral phenotypes was similar. The corticosteroid reaction was absent in animals with the "domesticated" type of behavior, while it was significantly pronounced in animals with a clear-cut behavioral reaction of withdrawal from a human ("wild" phenotype) at different ages. Sheep of the "wild" type of behavior were not uniform in the rate of the age-dependent decrease in withdrawal and stress reactions: these reactions were stable in individuals of "conservative" phenotypes. Thus, the ontogenetic formation of the long-term adaptation of the HPA axis of sheep to isolation depends on genetically determined behavior and factors, which control correlated changes in feeding and defensive reactions in animals of the "wild" phenotype.

Adaptation, Physiological↗

Social isolation, impulsivity and depression as predictors of aggression in a psychiatric inpatient population.

Aggressive behavior among psychiatric inpatients remains an issue of concern for staff, families and patients themselves. At the present time, studies examining prediction of aggression among psychiatric inpatients have focused mainly on diagnostic or demographic risk factors. Unfortunately little is known about specific social functioning and personality risk factors that may help identify specific individuals at risk for aggressive behavior. Given that many individuals who have engaged in violent criminal behavior have been observed to experience a combination of social isolation, depression and impulsiveness, it is possible that this same combination of traits may function as a predictor of aggression among psychiatric inpatients. The current study examines whether psychiatric inpatients with a combination of social isolation, depression and impulsivity are significantly more likely to become aggressive than other psychiatric inpatients without that combination of factors. Results indicated that impulsivity functioned as a positive predictor of aggression, whereas depression acted as a protective factor. Perceived social support did not appear to relate strongly to aggression. Further, physicians' ratings of hostility were more predictive of aggressive incidents than were self-reports of hostility. Clinical implications of these findings are discussed.

Adult↗

Post-weaning social isolation of rats leads to an abnormal gait.

The purpose of this study was to further characterize the phenotype of rats that have experienced prolonged postweaning social isolation, a paradigm that produces changes relevant to neuropsychiatric disorders. At weaning, male Wistar rats from three litters were housed socially (n = 12) or in isolation (n = 13) for 10 weeks. Isolated rats could see, hear and smell other rats. A sophisticated analysis of gait revealed that the stride duration was increased in isolates (12%, P = 0.0024) as a result of increased stance duration (18%, P = 0.0005), but there was no difference in vertical reaction force or velocity. Adrenal glands were heavier in isolates (19%, P = 0.0047). There was no difference in cross-sectional area of the brain or lateral ventricles anywhere along the anterior-posterior axis. All experiments and analysis were performed blind to housing condition. This is the first study to demonstrate that socially isolated rats have an abnormal gait. Further analysis, including pharmacological manipulation, is needed in order to understand the nature of the abnormality.

Adrenal Glands↗

Effects of social isolation on ehrlich tumor growth and tumor leukocyte infiltration in mice: evidence of participation of the submaxillary salivary gland.

OBJECTIVE: Considering previous studies on stress and Ehrlich tumor growth from our laboratory and also known cell growth and behavior-related properties of submaxillary salivary gland products, we studied the effects of stress by social isolation, in combination or not with sialectomy (submaxillary gland ablation), on growth and leukocyte infiltration into Ehrlich adenocarcinomas. METHODS: 5 x 10(7) tumor cells/ml were inoculated into the footpads of mice and tumor growth was evaluated by measuring paw thickness on alternate days. Ten days after inoculation, tumors were harvested and processed for immunocytochemical analysis of tumor-infiltrating leukocytes (TIL) and nerve-like growth factor (NGF)/epidermal growth factor (EGF)-positive tumor cells. T and B lymphocyte, NK cell and macrophage percentages were calculated. RESULTS: Sialectomy slightly reduced tumor growth and caused a significant increase in NK cell infiltration of tumors (p < 0.05). Social isolation caused a highly significant enhancement of both tumor growth (p < or = 0.05) and percentage of macrophages infiltrating tumors (p < 0.05). Sialectomized isolated animals showed few significant changes in tumor growth rate (p < or = 0.05), but presented increased percentages of NK cells, macrophages and B lymphocytes (p < 0.05). A reduction in the percentage of NGF+ tumor cells was also observed (p < 0.05). All of these effects were seen only in 8-month-old mice, but not in younger animals. CONCLUSION: A possible link between salivary gland factors, tumor growth and TIL patterns was considered, suggesting that growth factors may modulate tumor leukocyte infiltration as well as tumor growth rate.

Animals↗

Influence of social isolation, gender, strain, and prior novelty on plus-maze behaviour in mice.

Behavioural baseline is a critical determinant of response to drugs and other manipulations. In the present study, the influence of several organismic and procedural variables on basal plus-maze profiles in mice were examined. The methodology incorporated traditional behavioural parameters as well as novel measures derived from ethological analysis. Experiment 1 showed that social isolation for 1-3 weeks enhanced aggression in male DBA/2 mice but did not substantially alter their behaviour on the maze. A reduction in stretch attend postures did, however, suggest a minor reduction in anxiety in socially isolated animals. In Experiment 2, males of both DBA/2 and T1 strains exhibited higher levels of general activity on the maze than their female counterparts. Although additional evidence suggested that DBA/2 (but not T1) females were less anxious than males, no major sex differences were noted. Experiment 3 revealed a significant strain difference in plus-maze profiles, with T1 males showing a lower basal level of anxiety than DBA/2 males. This study also demonstrated that DBA/2 and T1 males react very differently to prior novelty experience, with enhanced anxiety evident in the former and reduced anxiety in the latter. Together, these findings point to a range of organismic and procedural variables that may account for inconsistencies in the literature on the elevated plus-maze.

Aggression↗

Social isolation: unit-based activities for impaired elders.

Loneliness can lead to illness and death, and is such a painful experience that a resident may not verbalize it directly. Quality nursing care requires that problems of social isolation are identified and a plan developed for adequate intervention. Impaired residents will be more successful socially when they can access a variety of interesting activities in small groups where familiar staff take initiative and establish a rapport. Institutional nurses are in a unique position to request the structural and personnel changes necessary to bring creative activities to the nursing units of impaired elders.

Aged↗

The selective mGlu5 receptor antagonist MTEP, similar to NMDA receptor antagonists, induces social isolation in rats.

It has repeatedly been shown that uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can mimic certain aspects of positive and negative symptoms of schizophrenia in human volunteers and laboratory animals. The purpose of the present study was to expand these findings and to determine whether the selective metabotropic glutamate receptor subtype 5 (mGluR5) antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine), could induce similar effects in Wistar rats. First, MTEP (1.0-10.0 mg/kg; intraperitoneally) after acute and subchronic (daily for 5 days) administration as well as the uncompetitive antagonists of the NMDA receptor of either high affinity, phencyclidine (0.5-4.0 mg/kg; subcutaneously (s.c.)) and (+)-MK-801 (0.03-0.25 mg/kg; s.c.), or low-moderate affinity, ketamine (2.0-16.0 mg/kg; s.c.) and memantine (0.15-20.0 mg/kg; s.c.), following daily administration for 3 days were tested in the social interaction test to determine their ability to reproduce the negative and positive symptoms measured by social isolation and stereotyped behavior, respectively. Second, the compounds were tested in the motility test following acute administration to determine their ability to induce locomotor hyperactivity reflecting the positive symptoms. In line with previous findings, all examined NMDA receptor antagonists produced social interaction deficits, locomotor hyperactivity, and stereotypy except memantine. Notably, this study found that MTEP following both acute and subchronic administration dose-dependently induced social isolation, but did not cause either locomotor hyperactivity or stereotypy. These data demonstrate that social behavior deficits in rats can be caused by both the blockade of the NMDA receptor and the inhibition of mGluR5, whereas mGluR5 antagonists may not independently be able to mimic the positive symptoms.

Analysis of Variance↗