Differential effects of social stress on central serotonergic activity and emotional reactivity in Lewis and spontaneously hypertensive rats

Social stress by repeated defeat has been shown to be endowed with neuroendocrine and behavioural effects that render this stress model useful to identify adaptive mechanisms. Among these mechanisms, those related to central serotonergic systems (e.g., hippocampal 5-HT1A receptors, cortical 5-HT2A receptors) have been particularly underlined. Nonetheless, how (i) the neuroendocrine and behavioural effects of social stress are affected by the genetic status of the animal, and (ii) this status affects the relationships between central serotonergic systems and adaptive processes has not been studied so far. The present study has thus analysed the effects of repeated defeat (once a day for seven days) by Long-Evans resident rats upon the psychoneuroendocrine profile of Lewis rats and spontaneously hypertensive rats previously characterized for their contrasting social and anxiety-related behaviours. Repeated defeat decreased in a time-dependent manner, body weight growth and food intake in both strains, these decreases being, however, more severe and longer lasting in Lewis rats. This strain-dependent difference could not be accounted for by differences in physical contacts with the resident rats as the number of attacks and their latency throughout the stress period were similar between spontaneously hypertensive and Lewis rats. When exposed to an elevated plus-maze test of anxiety, the unstressed Lewis rats entered less the open arms than their spontaneously hypertensive counterparts, thus confirming that Lewis rats are more anxious than spontaneously hypertensive rats. This difference was amplified by stress as the latter increased anxiety-related behaviours in Lewis rats only. These strain- and stress-related differences were associated with differences in locomotor activity, this being increased in unstressed Lewis compared with spontaneously hypertensive rats; moreover, stress triggered hypolocomotion in the former but not the latter strain. Lastly, in the forced swimming test. Lewis rats spent more time immobile than spontaneously hypertensive rats with stress increasing immobility in a strain-independent manner. Beside the aforementioned metabolic changes, the activity of the hypothalamo-pituitary-adrenal axis was slightly stimulated in a strain-independent manner by the stressor, as assessed by increased corticosterone levels and adrenal weights, and decreased thymus weights. In Lewis, but not in spontaneously hypertensive rats, midbrain serotonin metabolism was increased by stress, a difference associated with an increased Bmax value of cortical [3H]ketanserin binding at 5-HT2A receptors. On the other hand, the Bmax value of hippocampal [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding at 5-HT1A receptors was decreased by stress, this reduction being amplified in spontaneously hypertensive compared with Lewis rats. This study shows that the psychoneuroendocrine responses to social stress may have a genetic origin, and that the use of socially stressed Lewis and spontaneously hypertensive rats may provide an important paradigm to study adaptive processes. However, whether the aforementioned strain-dependent differences in central serotonergic systems (partly or totally) underlie the distinct profiles of emotivity measured in spontaneously hypertensive and Lewis rats, is discussed in the context of the relationships between serotonergic systems and behavioural responses to novel environments.     

Chronic parenting stress: Moderating versus mediating effects of social support.

Contrasted the widely cited "buffer" model of social support with an alternative mediator model. Distinctions were drawn between the functions of social support under chronic vs acute stress conditions, and between situation-specific stressors and major life events. Ongoing parenting stress was assessed in 96 mothers of deaf children and 118 matched controls. Tests of the competing models showed no moderating effects for social support. However, path analyses suggested that social support mediated the relationship between stressors and outcomes. Chronic parenting stress was associated with lowered perceptions of emotional support and greater symptoms of depression and anxiety. Furthermore, parenting stress accounted for a substantial proportion of the variance in psychological distress scores in contrast to life event stress, which was only weakly related to psychological outcomes. The implications of mediational models for understanding adaptation to chronic stress are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Noradrenergic and serotonergic function in posttraumatic stress disorder

BACKGROUND: Yohimbine hydrochloride produces marked behavioral and cardiovascular effects in combat veterans with posttraumatic stress disorder (PTSD). In the present study, yohimbine was used as a probe of noradrenergic activity, and meta-chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our knowledge, this is the first study to describe the behavioral and cardiovascular effects of meta-CPP in patients with PTSD, and to compare these effects with those of yohimbine. METHOD: Twenty-six patients with PTSD and 14 healthy subjects each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m-CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized balanced order and in double-blind fashion. Behavioral and cardiovascular measurements were determined at multiple times. RESULTS: Eleven (42%) of the patients with PTSD experienced yohimbine-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with PTSD experienced m-CPP-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, and in standing diastolic blood pressure. Yohimbine-induced panic attacks tended to occur in different patients from m-CPP-induced panic attacks. CONCLUSION: These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.     

Effects of social isolation and social separation in domestic chicks.

Conducted 2 experiments with 60 white Leghorn chicks, with subsamples of 24 and 36 animals tested in 2 independent replications, to assess the impact of early social isolation and social separation on the behavior of domestic chicks. In Exp I, a 3-wk longitudinal study, the day-to-day behavior of isolated chicks was compared to the behavior of birds housed in pairs. Ss in a 3rd group were reared in pairs for 2 wks, and then were permanently separated. The daily observations of all Ss recorded disturbance reactions, exploratory activities, consummatory behavior, grooming, and inactivity. In Exp II, 36 Ss from the 3 experimental conditions were tested in the 4th posthatch week for general social responsiveness in the presence of unfamiliar conspecifics. Results show that (a) both isolation and separation produced behavioral anomalies; (b) separated Ss' reactions indicated patterns analogous to post-separation patterns seen in other species; and (c) the effects of isolation and separation were not qualitatively equivalent--exposure to conspecifics revealed antisocial behavior in the isolates, relative to the responses of their socially reared and separated counterparts. Results are discussed in terms of a model for differences in the essence and consequences of early social isolation and social separation. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of corticotropin-releasing factor on brain serotonergic activity

The serotonergic dorsal raphe nucleus is innervated by corticotropin-releasing factor (CRF) and expresses CRF receptors, suggesting that endogenous CRF impacts on this system. The present study characterized interactions between CRF and the dorsal raphe serotonin (5-HT) system. The effects of intracerebroventricularly (i.c.v.) administered CRF on microdialysate concentrations of 5-HT in the lateral striatum of freely moving rats were determined. CRF had biphasic effects, with 0.1 and 0.3 microgram decreasing, and 3.0 micrograms increasing 5-HT dialysate concentrations. i.c.v. administration of CRF inhibited neuronal activity of the majority of dorsal raphe neurons at both low (0.3 microgram) and high (3 micrograms) doses. Likewise, intraraphe administration of CRF (0.3 and 1.0 ng) had predominantly inhibitory effects on discharge rate. Together, these results suggest that CRF is positioned to regulate the function of the dorsal raphe serotonergic system via actions within the cell body region. This regulation may play a role in stress-related psychiatric disorders in which 5-HT has been implicated.     

Drinking your troubles away: The role of activity in mediating alcohol's reduction of psychological stress.

Two experiments with 133 undergraduates tested the hypothesis that alcohol's reduction of psychological stress depends to an important degree on whether the drinker is also engaged in distracting activity. In Study 1, the factor of whether Ss had received alcohol (1 mg/kg) was crossed, in a 2?×?2 design, with the factor of whether they rated pleasant art slides or did nothing during a period that immediately followed their having received negative feedback on an IQ test (taken earlier). As predicted, a significant interaction effect showed that mood improvement during this recovery period was greatest in the alcohol/slides condition—the only condition in which absolute mood improvement reached significance. Study 2 replicated this effect, ruling out several alternative explanations of the alcohol–activity effect. The implication that alcohol's reduction of psychological stress stems largely from its impairment of cognitive processes that, in conjunction with distracting activity, blocks out stress-inducing thoughts is discussed. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of corticotropin releasing hormone on the pituitary-adrenocortical activity under basal and social stress conditions

The effect of social crowding stress on the CRH-induced hypothalamic-pituitary-adrenocortical (HPA) responsiveness was assessed in rats crowded for 3 days, when the HPA response to neurotransmitter receptors stimulation was powerfully reduced. CRH given systemically dose-dependently increased the secretion of corticosterone. The increase was not affected by pretreatment with prazosin or propranolol, an alpha 1- or beta-adrenergic receptor antagonist, indicating the lack of involvement of adrenergic receptors in that stimulation. In the corticosterone response to CRH administered icv, a moderate involvement of hypothalamic alpha 1-adrenergic receptors and neuronal noradrenaline seems possible. The corticosterone responses to CRH given by either route to rats exposed to social crowding stress were identical with the responses of unstressed controls. Our results for the first have time shown that social crowding stress does not impair the HPA responsiveness to CRH stimulation.     

Regional brain electrical activity in posttraumatic stress disorder after motor vehicle accident.

This study examined whether patients with posttraumatic stress disorder (PTSD) related to motor vehicle accidents (MVAs) would show an abnormal pattern of electroencephalographic (EEG) alpha asymmetries, which has been proposed for particular types of anxiety. Patients with PTSD (n = 22) or subsyndromal PTSD (n = 21), traumatized controls without PTSD (non-PTSD with MVA; n = 21), and healthy controls without MVA (n = 23) underwent measurement of EEG activity during baseline and exposure to a neutral, a positive, a negative, and an accident-related picture. Differences in brain asymmetry between groups were observed only during exposure to trauma-related material. PTSD and subsyndromal PTSD patients showed a pattern of enhanced right anterior and posterior activation, whereas non-PTSD with MVA participants showed the opposite pattern. Furthermore, posterior asymmetry in nontraumatized healthy controls varied with gender, with female participants showing a pattern of higher right posterior activation. The results support the hypothesis that symptomatic MVA survivors are characterized by a pattern of right hemisphere activation that is associated with anxious arousal and symptoms of PTSD during processing of trauma-specific information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An investigation into the psychobiology of social phobia: personality domains and serotonergic function

The high-molar mass form of beta-glucosidase from Aspergillus niger strain NIAB280 was purified to homogeneity with a 46-fold increase in purification by a combination of ammonium sulfate precipitation, hydrophobic interaction, ion-exchange and gel-filtration chromatography. The native and subunit molar mass was 330 and 110 kDa, respectively. The pH and temperature optima were 4.6-5.3 and 70 degrees C, respectively. The K(m) and kcat for 4-nitrophenyl beta-D-glucopyranoside at 40 degrees C and pH 5 were 1.11 mmol/L and 4000/min, respectively. The enzyme was activated by low and inhibited by high concentrations of NaCl. Ammonium sulfate inhibited the enzyme. Thermolysin periodically inhibited and activated the enzyme during the course of reaction and after 150 min of proteinase treatment only 10% activity was lost with concomitant degradation of the enzyme into ten low-molar-mass active bands. When subjected to 0-9 mol/L transverse urea-gradient-PAGE for 105 min at 12 degrees C, the nonpurified beta-glucosidase showed two major bands which denatured at 4 and 8 mol/L urea, respectively, with half-lives of 73 min.     

Residential density and psychological health: The mediating effects of social support.

People report excessive, unwanted social interactions, insufficient privacy, and are observed to be more socially withdrawn under crowded living conditions. If people socially withdraw from one another as a way to cope with crowding, this could lead to an unintended side effect of breakdowns in socially supportive relationships. A breakdown in socially supportive relationships could, in turn, account for some of the pathological consequences of chronic, high density living conditions. An empirical study of 175 male heads of household among inner city residents in India suggests that the adverse effects of residential crowding on psychological health are mediated by a breakdown of social support systems. The study also points to the value of examining social support as an endogenous variable in the stress and health process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The temporal dynamics of the stress response

This paper summarises the available evidence that failure of defense mechanisms in (semi)-natural social groups of animals may lead to serious forms of stress pathology. Hence the study of social stress may provide animal models with a high face validity. However, most of the animal models of human stress-disorders have concentrated on the consequences of chronic exposure to stressors. The present paper considers recent data, indicating that a single experience with a major stressor in the form of social defeat may have long-term consequences ranging from hours to days and weeks. It seems that the experience of a major stressor sensitizes the animal to subsequent stressors. The consequences of these long-term temporal dynamics of the stress response to the development of stress-related disorders and stress-vulnerability are discussed.     

Hyperbolic temporal discounting in social drinkers and problem drinkers.

Two studies compared participants, distinguished by their typical alcohol consumption, on the degree to which they discounted the value of delayed, hypothetical amounts of money. Heavy social drinkers in Study 1 and problem drinkers in Study 2 both showed greater temporal discounting than light social drinkers; this difference was stronger in Study 2. Both studies found that a hyperbolic function described temporal discounting more accurately than an exponential function. These results are consistent with extending behavioral theories of intertemporal choice to characterize the determinants of alcohol consumption. The discounting differences also are consistent with more general behavioral economic and economic theories of addiction, although the hyperbolic functional form is inconsistent with the exponential discounting function in economic theory. The drinker groups also differed on impulsiveness and time orientation questionnaires, with light drinkers being less impulsive and more future oriented; however, these measures were not strongly correlated with the measure of temporal discounting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Actions of serotonergic agents on hypothalamic-pituitary-adrenal axis activity in the rat

1. The effects of ipsapirone, nefazodone, tiaspirone, BMS-20661, buspirone and gepirone on the hypothalamic-pituitary-adrenal (HPA) axis were studied. These drugs were selected because they have serontonin 1A (5-HT1A) receptor-binding capability and have the potential for therapeutic activity in the treatment of major affective or anxiety disorders or both. 2. Plasma corticosterone level was used as the end point for determining the effect of each drug on the HPA axis. Each drug increased the plasma corticosterone levels in a dose-dependent manner. The ED50 values were 0.8 mg/kg for BMS-20661, 3.5 mg/kg for gepirone, 3.9 mg/kg for buspirone, 5.3 mg/ kg for tiaspirone, 10.5 mg/kg for ipsapirone and 73.5 mg/kg for nefazodone. Ipsapirone and buspirone were more efficacious than the other four drugs. 3. The effect of a 10-mg/kg (35 mg/kg for nefazodone) test dose of each drug reached a peak between 30 min and 1 hr, and plasma corticosterone levels generally returned to control levels after 2 hr. 4. When the drugs were given 30 min before decapitation, in conjunction with a rotatory stress, BMS-20661 significantly inhibited the stress-induced rise, whereas ipsapirone and gepirone caused a significant increase in plasma corticosterone levels. However, when the drugs were given 2 hr before decapitation, nefazodone caused a significant decrease, whereas ipsapirone, BMS-20661 and gepirone produced significant increases in HPA axis activity. An 0800 hr dose of 0.1 mg/kg of dexamethasone suppressed the 1500 hr HPA activity by 73.1%. The 0.1-mg/kg dose of dexamethasone significantly reduced the drug-activated HPA axis activity of all of the drugs from their saline-control levels. The rank order, from least to greatest inhibitory effect, produced by this dexamethasone treatment on the drug-control levels was gepirone (-42.6%), tiaspirone (-48.9%), buspirone (-56.1%), nefazodone (-68.5%), insapirone (-70.0%), and BMS-20661 (-74.3%).     

Enhancement of serotonergic neural activity contributes to cyclosporine-induced tremors in mice

Patients suffering from inflammatory or dysimmunitary diseases may develop various clinical responses to corticotherapy. This brief article describes the various cellular and molecular mechanisms which underly the genetic, endocrine and immunitary factors involved in corticosensitivity, corticoresistance and corticodependence.     

An investigation of the effects of maternal separation and novelty on central mechanisms mediating pituitary-adrenal activity in infant guinea pigs (Cavia porcellus).

In mammalian species in which the young exhibit a strong filial attachment (e.g., monkeys, guinea pigs), numerous studies have shown that even brief separation from the attachment figure potently elevates circulating concentrations of glucocorticoids and adrenocorticotropic hormone (ACTH). However, effects of separation on central regulation of this stress response are not known. Therefore, we investigated central mechanisms mediating pituitary-adrenal activation during maternal separation and novelty exposure in guinea pig (Cavia porcellus) pups. Corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN), and plasma cortisol and ACTH levels, were elevated only during separation in a novel environment. C-Fos activity was elevated in the medial amygdala (MeA) and reduced in the bed nucleus of the stria terminalis (BNST) during novelty exposure, regardless of separation. On the other hand, c-Fos activity was elevated in the PVN during separation, regardless of novelty exposure. These results demonstrate independent and combined effects of separation and novelty in regions of the guinea pig CNS that regulate pituitary-adrenal activity. Moreover, they suggest that a pathway from MeA to BNST to PVN mediates responses to novelty in the guinea pig pup, as in the adult rat, though inputs from other cell populations appear required to fully account for the HPA activity observed here. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intergenerational continuity in parenting quality: The mediating role of social competence.

Prospective studies of intergenerational continuity in parenting quality remain scarce, with little attention given to the potential role of social competence as a mediator of continuity. This study examined social competence as a mediator in the pathway from 1st generation (G1) to 2nd generation (G2) parenting quality. A normative sample of children and their parents were assessed in childhood, and again 10 and 20 years later. Parenting quality of G1 parents was assessed at each time point with multiple informants, as was G2 social competence. G2 parenting was assessed at the 20-year follow-up for those who were parents. The mediational role of social competence in G1 to G2 parenting quality was tested via nested path analytic models, accounting for continuity and cross-domain relations. Social competence mediated the intergenerational relation of parenting quality; results were invariant across gender and ethnic minority status and were unchanged after controlling for age, IQ, socioeconomic status, rule-abiding conduct, and personality (i.e., constraint). The authors discuss results regarding developmental theories of close relationships and the potential for cascading benefits within and across generations from interventions to improve G1 parenting or G2 social competence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality and social resources in stress resistance.

Examined personality, social assets, and perceived social support as moderators of the effects of stressful life events on illness onset. In a group of 170 middle- and upper-level male executives (aged 32–65 yrs), personality hardiness (assessed by 3 scales of the Alienation Test, the Security scale of the California Life Goals Evaluation Schedule, and Rotter's Internal–External Locus of Control Scale) and stressful life events (an adaptation of the Schedule of Recent Events) consistently influenced illness scores, the former serving to lower symptomatology (Seriousness of Illness Survey), the latter to increase it. Perceived supervisor support had its predicted positive effect. Executives under high stress who perceived support from their supervisors had lower illness scores than those without support. Perceived family support, on the other hand, showed a negative effect on health when reported by those low in hardiness. Social assets made no significant impact on health status. Results underscore the value of differentiating between types of social resources and of monitoring the effects of 2 or more stress-resistance resources in a single study. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Roles of suprachiasmatic nuclei and intergeniculate leaflets in mediating the phase-shifting effects of a serotonergic agonist and their photic modulation during subjective day

Serotonin (5-HT) has been implicated in the phase adjustment of the circadian system during the subjective day in response to nonphotic stimuli. Two components of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian clock) and the intergeniculate leaflet (IGL), receive serotonergic projections from the median raphe nucleus and the dorsal raphe nucleus, respectively. Experiment 1, performed in golden hamsters housed in constant darkness, compared the effects of bilateral microinjections of the 5-HT1A/7 receptor agonist, 8-hydroxydipropylaminotetralin (8-OH-DPAT; 0.5 microgram in 0.2 microliter saline per side), into the IGL or the SCN during the mid-subjective day. Bilateral 8-OH-DPAT injections into either the SCN or the IGL led to significant phase advances of the circadian rhythm of wheel-running activity (p < .001). The phase advances following 8-OH-DPAT injections in the IGL were dose department (p < .001). Because a light pulse administered during the middle of the subjective day can attenuate the phase-resetting effect of a systemic injection of 8-OH-DPAT, Experiment 2 was designed to determine whether light could modulate 5-HT agonist activity at the level of the SCN and/or the IGL. Serotonergic receptor activation within the SCN, followed by a pulse of light (300 lux of white light lasting 30 min), still induced phase advances. In contrast, the effect of serotonergic stimulation within the IGL was blocked by a light pulse. These results indicate that the respective 5-HT projections to the SCN and IGL subserve different functions in the circadian responses to photic and nonphotic stimuli.     

Intoxication and exposure to stress: Effects of temporal patterning.

In this study we explored the temporal patterning of intoxication and exposure to a stress-producing situation on alcohol's effects on stress. 40 male social drinkers received either a 0.7 g/kg dose of alcohol or a placebo. When exposure to a social stressor preceded intoxication, a significant alcohol-induced increase in heart-rate reactivity was found. When intoxication preceded exposure to the stressor, conventional analysis of the data indicated a stress-dampening effect of alcohol on heart rate. No differences were obtained from self-reports of anxiety in either pattern. The findings are explained in terms of attentional and cognitive-encoding processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Community violence exposure and children's social adjustment in the school peer group: The mediating roles of emotion regulation and social cognition.

This study reports a cross-sectional investigation of the relation between community violence exposure and peer group social maladjustment in 285 inner-city children in Grades 4–6 (mean age?=?10.3 years). Children completed an inventory assessing exposure to community violence through witnessing and through direct victimization. A peer nomination inventory was then administered to assess social adjustment with peers (aggression, peer rejection, and bullying by peers). In addition, social-cognitive biases and emotion regulation capacities were examined as potential mediators. Analyses indicated that violent victimization was associated with negative social outcomes through the mediation of emotion dysregulation. Witnessed violence was linked only to aggressive behavior. Social information processing, rather than emotion dysregulation, appeared to mediate this association. These results demonstrate that violence exposure is linked to multiple levels of behavioral and social maladjustment and suggest that there are distinct patterns of risk associated with different forms of exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)