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Neuropharmacological actions of Pluchea indica Less root extract in socially isolated mice.

The effects of Pluchea indica Less root extract (PI-E) on locomotor activity and pentobarbital-induced sleep, social isolation-induced aggressive behavior, motor coordination in the rotarod test, pentylenetetrazole-induced convulsion and nociceptive responses in the tail-pinch test were examined in mice. Socially isolated mice showed higher locomotor activity and shorter duration of pentobarbital sleep than group-housed mice. PI-E (50-100 mg/kg, p.o.) significantly decreased locomotor activity and prolonged pentobarbital sleep in a dose-dependent manner in isolated mice but not in group-housed mice. At a large dose (400 mg/kg, p.o.), PI-E not only decreased locomotor activity but also prolonged pentobarbital sleep in group-housed mice. The reference drug diazepam, at 0.5 mg/kg, also suppressed the locomotor activity in isolated mice but not in group-housed mice. Moreover, diazepam, at 0.1 and 0.5 mg/kg, significantly prolonged pentobarbital sleep in both isolated mice and group-housed mice. The effects of PI-E and diazepam on pentobarbital sleep in isolated mice were significantly attenuated by flumazenil (1 mg/kg, i.v.). PI-E (50-100 mg/kg), as well as diazepam (0.5-5 mg/kg, p.o.), dose-dependently suppressed social isolation-induced aggressive behavior, but it had no effect on pentylenetetrazole-induced convulsion, motor coordination in the rotarod test, or nociceptive response in the tail pinch test in group-housed mice. These results suggest that PI-E attenuates pathophysiological changes caused by social isolation stress in mice, and that the GABAergic system is partly involved in the action of PI-E on a social isolation-induced decrease in pentobarbital sleep.

Aggression↗

Investigation of changes in global gene expression in the frontal cortex of early-weaned and socially isolated piglets using microarray and quantitative real-time RT-PCR.

We hypothesize that early-weaned piglets experience aberrant expression of stress-responsive genes in the frontal cortex, a key brain area involved in cognitive function and behavior organization. To test this hypothesis, female early-weaned piglets (EW; n = 6) were weaned 10 days after birth, while non-weaned piglets (NW; n = 6) were left with their dams. Half of EW (n = 3) and NW (n = 3) animals were socially isolated (SI) for 15 min at 12 days of age, when all animals (n = 12) were euthanized and tissue collected. The effects of EW and SI were examined by gene expression profiling using cDNA microarray hybridizations, generated from a porcine brain cDNA library. A total of 103 genes were differentially expressed (P < 0.05, fold change >1.25) among four direct comparisons. Forty-two genes had known functions, from which 24 showed relevant brain-related functions. Quantitative real-time polymerase chain reaction (Q-RT-PCR) was used to confirm regulation of expression of a subset of 6 genes with important brain functions, selected from the microarray outcomes. In non-weaned animals, a significant suppression of mRNA abundance for carboxypeptidase E, 14-3-3 protein and phosphoprotein enriched in astrocytes 15 kDa was observed in response to SI. Also, in early-weaned animals, diazepam binding inhibitor and actin-related protein 2/3 complex mRNA levels were suppressed in response to SI. Results suggest that social isolation of non- and early-weaned piglets may impact expression of genes involved in regulation of neuronal function, development, and protection in the frontal cortex of young pigs.

Animals↗

Social isolation from communities and child maltreatment: a cross-cultural comparison.

OBJECTIVE: The aim of this study is to determine: (1) the differences between Spanish and Colombian cultures in relation to community social support variables, and (2) the relationships between community social support variables and child maltreatment in both cultures. METHOD: The study was based on 670 nonabusive families and 166 abusive families. The parents were asked to complete the Community Social Support Questionnaire. This instrument measures community social support in terms of Community Integration and Satisfaction, membership in voluntary organizations and community participation, and use of Community Resources of Social Support. RESULTS: Differences between both cultures were found in the pattern of community social support for the nonabusive groups. However, the relationships between community social support and child maltreatment were similar cross-culturally. Our results indicate that in both cultures abusive parents show lower levels of community integration, participation in community social activities and use of formal and informal organizations than the parents that provide adequate care. CONCLUSIONS: The results largely support the literature that has repeatedly reported the link between social isolation and child maltreatment and they confirm this relation within two cultural contexts, Colombian and Spanish, quite different from the Anglo-Saxon context, where most of the previous studies have been carried out.

Adult↗

The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders.

Allopregnanolone (3alpha,5alpha-TH PROG) and 5alpha-dihydroprogesterone (5alpha-DH PROG), the two most important neuroactive steroids synthesized in the brain, potently modulate neuronal activity by allosterically regulating GABA action at GABA(A) receptors or by changing specific GABA(A) receptor subunit gene expression, respectively. We recently reported [Proc. Natl. Acad. Sci. USA 95 (1998) 3239] that in patients with severe depression there is a decrease in the CSF levels of 3alpha,5alpha-TH PROG, which is normalized by treatment with drugs (i.e. fluoxetine) that improve psychopathology. The mechanism by which fluoxetine and other selective serotonin reuptake inhibitors normalize 3alpha,5alpha-TH PROG CSF levels appears to involve a direct stimulation of 3alpha-hydroxysteroidoxidoreductase (3alpha-HSD), an enzyme that catalyses the reduction of 5alpha-DH PROG into 3alpha,5alpha-TH PROG. Here, we propose the use of socially-isolated mice that have a downregulation of 3alpha,5alpha-TH PROG and of 5alpha-DH PROG expression to establish a model to study the behavioral consequences of this deficiency. After 4-6 weeks of isolation, these mice exhibit increased anxiety and aggressive behavior and also a decreased response to the administration of GABA-mimetic drugs. In these mice, the decrease in 3alpha,5alpha-TH PROG is selectively normalized by the use of fluoxetine in doses that reduce behavioral abnormalities. In addition, the expression of 5alpha-reductase Type I mRNA and protein was lower in socially-isolated mice than that in group-housed mice whereas 3alpha-HSD mRNA expression remained unchanged. The results of these studies may enable us to design drugs that specifically affect neurosteroidogenic enzymatic activities and may provide an efficacious treatment for the psychopathologies associated with psychiatric disorders.

20-alpha-Dihydroprogesterone↗

Early social isolation of the domestic cat: responses to separation from social and nonsocial rearing stimuli.

The relative contributions of social-rearing stimuli (a mother and/or a littermate) and nonsocial-rearing stimuli (a brooder) to the formation and decline of infant kitten attachments were assessed by counting the frequency of distress cries produced by separation from the following rearing conditions: (1) mother-littermate; (2) mother-only; (3) brooder-littermate; and (4) brooder-only. Four male and 4 female kittens were reared in each condition. Each kitten was separated from its rearing condition once a week, from 2 until 5 weeks of age, and placed in open field for 15 min. The frequency of distress cries in both littermate-reared groups did not significantly differ throughout the experiment. The frequency was consistently high until 5 weeks of age when distress cries were significantly reduced. The frequency of distress cries consistently increased in the mother-only-reared kittens with repeated separations, but consistently decreased in the brooder-only-reared kittens. The results were interpreted as being commensurate with the social conditions at the time of separation.

Animals↗

Social isolation and aggressiveness in the Amazonian juvenile fish Astronotus ocellatus.

We tested the effect of social isolation on the aggressiveness of an Amazonian fish: Astronotus ocellatus. Ten juvenile fishes were transferred from a group aquarium (60 x 60 x 40 cm) containing 15 individuals (without distinguishing sex) to an isolation aquarium (50 x 40 x 40 cm). Aggressiveness was tested by means of attacks on and displays toward the mirror image. The behavior was video-recorded for 10 min at a time on 4 occasions: at 30 min, 1 day, 5 days and 15 days after isolation. The aggressive drive was analyzed in three ways: latency to display agonistic behavior, frequency of attacks and specific attacks toward the mirror image. The latency to attack decreased during isolation, but the frequency of mouth fighting (a high aggressive attack) tended to increase, indicating an augmented aggressive drive. Our findings are congruent with the behavior of the juvenile cichlid, Haplochromis burtoni but differ from the behavior observed in another cichlid, Pterophylum scalare. Increased aggressiveness in A. ocellatus may be mediated by means of the primer effect, the effect of prior residence or processes involving recognition of a conspecific.

Aggression↗

Using positive peer reporting to improve the social interactions and acceptance of socially isolated adolescents in residential care: a systematic replication.

We studied how rewarding youth in residential care for publicly reporting positive social behavior influenced the social interactions and acceptance of their most socially isolated peers. Results showed that the intervention resulted in substantial improvements in social interactions by the previously isolated peers. Peer acceptance ratings also improved for 2 of the target youths.

Adolescent↗

Effects of social isolation and crowding upon adrenocortical reactivity and behavior in the rat.

The effects of social isolation and crowding on adrenocortical function and upon behavioral responsiveness to electric shock have been studied in male and female rats. All female experimental groups showed higher corticosterone levels and heavier adrenals than their male counterparts. The major effect of housing condition concerned the corticosterone response to stress, while basal hormone concentration was not modified. Socially housed rats showed a more intense adrenocortical response and also a greater behavioral reactivity to electric shock than the isolates.

Adrenal Glands↗

Social isolation modifies the response of mice to experimental Mengo virus infection.

To investigate the effects of social isolation on host resistance male mice were housed either individually (IH) or in groups of four or five (GH). All animals were infected with MengoM,L virus. Incubation time (INCUB), duration of illness (ILL), death rate (DR), histopathological changes, and serum corticosterone levels (CORT) were recorded. First, the effect of IH starting 4 days prior to infection was studied in 5 different inbred strains. Next, the effect of different IH length was examined, and the role of T-cells was investigated by comparing euthymic (+/+) and athymic (nu/nu) NMRI mice. Finally, the effects of the infection on CORT in IH and GH mice were compared in C57BL/6 mice. The major findings were: 1. IH significantly increased ILL in all but the DBA/2 strain, whereas DR was not affected except in C57BL/6. 2. Longer IH (starting 35 [DBA/2] or 10 [NMRI] days prior to virus inoculation) significantly shortened INCUB and prolonged ILL, but IH starting on the day of virus inoculation [DBA/2] significantly prolonged INCUB and shortened ILL. 3. NMRI nude mice exhibited an unaltered DR accompanied by a tremendously prolonged INCUB. 4. Investigations in C57BL/6 mice revealed a significant rise of CORT after infection. This increase was higher in IH compared to GH mice. It is suggested that IH attenuates T-cell mediated inflammatory processes and/or increases macrophage activation, which in turn results in a prolonged course of the disease.

Animals↗

[The dynamics of behavioral changes in mice induced by social isolation].

Various behavioural patterns such as spontaneous locomotion, open-field behaviour and aggressivity undergo typical changes in socially isolated mice. Each of them shows a specific course depending on the duration of isolation. Differences in time courses and quantitative changes demonstrate that not only a general mechanism such as decreased arousal threshold is responsible for the complex alterations. It seems that many different mechanisms in the CNS underly the isolation syndrome, but the functional connections between the different alterations are unknown.

Aggression↗

Effects of social isolation on pentobarbital activity in mice: relationship to racemate levels and enantiomer levels in brain.

The effects of social isolation on hypnotic actions induced by pentobarbital (PB) were investigated pharmacokinetically in isolated and aggregated mice and rats. Animals were administered i.p. 50 mg/kg of sodium (+-)-PB, S(-)-PB or R(+)-PB. Experiments in mice indicated that the duration of sleep induced by sodium (+-)-PB was reduced in the isolated mice, while the onset of sleep or the (+-)-PB brain levels at the time of awakening did not differ significantly between isolated and aggregated mice. These results suggest that changes in pharmacokinetics of PB may underlie the difference in duration of sleep between isolated and aggregated mice. In additional experiments in mice, brain concentrations of (+-)-PB, S(-)-PB or R(+)-PB were determined at predetermined intervals after injection. These experiments demonstrated that the brain concentrations of (+-)-PB, as well as those of S(-)-PB, at each predetermined timepoint in mice sacrificed before awakening were significantly lower in the isolated mice. The brain R(+)-PB levels in the isolated mice were also significantly lower as compared with those in the aggregated mice at each timepoint after injection. Experiments in rats indicated that urinary 3'-hydroxypentobarbital (major metabolite) concentrations were higher in the isolated rats at 0 to 6 hr after injection, suggesting an increased rate of hepatic drug metabolism in the isolated rats. Take together, these findings suggest that an increased rate of metabolism of PB, especially that of the S(-)-enantiomer which is responsible for hypnotic action, in isolated rodents may be involved in the shorter duration of sleep time induced by sodium (+-)-PB.

Animals↗

Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia.

Phencyclidine (PCP) can induce a model psychosis in humans that mimics the positive and negative symptoms of schizophrenia. The purpose of the present study was to determine whether PCP can induce similar behavioural effects in rats and whether these effects can be alleviated by neuroleptic drug treatment. Rats were tested in the social interaction test, and their behaviour was quantified by an automated video-tracking system and manual scorings of stereotyped behaviour and ataxia. The behavioural effects of different dose- and administration regimes of PCP were initially determined, and it was found that PCP dose-dependently induced stereotyped behaviour and social isolation in the rats. Comparison to clinical studies suggests that these behaviours correspond to certain aspects of the positive and negative symptoms, respectively, of a PCP psychosis in humans. Subsequently, the effects of 3 or 21 days of administration of the antipsychotic drugs haloperidol or clozapine on the behaviour of either vehicle- or PCP-treated rats were determined. Haloperidol did not produce a selective antagonism of PCP, whereas chronic clozapine selectively inhibited the PCP-induced stereotyped behaviour and social isolation. These effects of haloperidol and clozapine suggest that this animal model can determine the effects of neuroleptic drugs on positive and negative symptoms, onset of action, and side-effect profile, including effects on the motor system. Together these data suggest that this may be a possible animal model of the positive and negative symptoms of schizophrenia.

Journal Article↗

The relationship of Internet use to depression and social isolation among adolescents.

The present study investigated whether higher levels of Internet use are associated with depression and social isolation among adolescents. Eighty-nine high school seniors were administered a questionnaire that measured low (less than 1 hour per day), moderate (1-2 hours per day), and high (more than 2 hours per day) Internet use; relationships with mother, father, and peers; and depression. Low Internet users, as compared with high users, reported better relationships with their mothers and friends.

Adolescent↗

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats.

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.

Adrenal Glands↗

[The anxiogenic activity of phenylethylamine in the social isolation test on mice].

One-day isolation of male albino mice of SHR strain significantly increased the level of social behaviour measured by the number and total duration of active contacts (sniffings). A putative endogenous anxiogen beta-phenylethylamine (5-12.5 mg/kg) inhibited the communication like human anxiogens corazole (10 mg/kg) and caffeine (200 mg/kg). Diazepam (1 mg/kg) prevented the action of phenylethylamine, phenibut (10-50 mg/kg) exerted no effect on it. The social isolation test during studying anxiogens and anxiolytics can be performed on mice as previously on rats.

Animals↗

In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine.

Social isolation (SI) of male mice lasting >4 weeks is associated with aggression toward intruders and a down-regulation of brain allopregnanolone (Allo) content. SI of female mice fails to down-regulate brain Allo content or to induce aggressiveness. Fluoxetine (Prozac in clinical use) is an S- and R-fluoxetine (FLX) mixture, which in mammals is metabolized into S- and R-norfluoxetine (NFLX). The S isomers of FLX and NFLX are more active than their respective R isomers in normalizing brain Allo down-regulation and in reducing the aggressiveness induced by SI. Thus, FLX stereospecifically reduces brain Allo down-regulation and the aggressiveness induced by SI, whereas serotonin (5-HT) uptake inhibition lacks stereospecificity. The doses of S-FLX and S-NFLX that reduce aggressiveness and Allo brain content down-regulation induced by SI are at least one order of magnitude lower than the doses that block 5-HT reuptake. Doses of imipramine that inhibit 5-HT uptake neither reduce aggressiveness nor normalize brain Allo down-regulation. We conclude that Allo brain content normalization is a better candidate than 5-HT reuptake inhibition to explain the reduction of aggressiveness elicited by S-FLX and S-NFLX.

Aggression↗

Combating the social isolation of chronic mental illness.

1. The diminished mental and emotional resources suffered by those with chronic mental illness (CMI) often lead to impoverished relationships that fail to produce satisfying connections with others. As a result, persons with CMI are frequently chronically lonely. 2. Moreno's sociometric principles and psychodramatic techniques for group therapy provide ways to increase interconnectedness with others by interrupting the self-reinforcing aspects of social isolation. 3. Role reversal, self-presentation, psychodramatic encounter, and sociometric exercises facilitate expanded emotional repertoire, let members know each other, provide relief from emotional distress, and produce information about the group needed to generate interaction.

Affect↗

Facets of support related to well-being: quantitative social isolation and perceived family support in a sample of elderly women.

The purpose of this study was to examine the independent and interactive relationships of measures of network embeddedness and perceived social support with mental and physical health measures from responses of a sample of 271 community-dwelling elderly women. Quantitative social isolation was measured as the co-occurrence of low network embeddedness with family and with friends. There was a threshold effect such that quantitatively isolated participants had poorer psychological well-being and functional health than did nonisolated participants. This effect was independent of perceived support levels. The pattern was different for perceived social support. Elderly women with low perceived family support had poorer psychological well-being regardless of perceived support from friends or network embeddedness. Implications are discussed for several unanswered questions in the social support literature, including possible interventions for the quantitatively isolated and for those with low levels of perceived support.

Aged↗