Social status in mice: behavioral, endocrine and immune changes are context dependent.

The aim of the present study was to investigate the effect of social status on the endocrine, immune and behavior response of male mice. We found that in mice reared in a group of siblings since weaning, no difference exists between dominants and subordinates in basal corticosterone level, in behavior in the open-field test (OFT) and in a series of immune parameters. These results suggest that living with siblings is not a stressful condition for either dominant or subordinate mice. Therefore, group-housed siblings can be regarded as a valid control group in social stress studies. When mice were subjected to chronic psychosocial stress for 21 days, four types of social outcome occurred: residents becoming dominants, intruders becoming subordinates, residents becoming subordinates and intruders becoming dominants. Interestingly, the behavioral profile in the OFT revealed a status-dependent effect, with resident dominants (RD) and intruder dominants (InD) showing the highest locomotor and exploratory activity, whereas the corticosterone level was higher than control for all four categories. In addition, a context-dependent effect emerged at the immune level: resident subordinates (RS) had a reduced splenocyte proliferation and IL-4 and IL-10 production. Mice in all the other three social ranks showed no immune alterations. Therefore, the loss of an individual's social rank position seems a promising field of study to investigate the psychological impact of stressful events.     

Social status differentiates rapid neuroendocrine responses to restraint stress

Male Anolis carolinensis that win aggressive interactions mobilize neuroendocrine responses to social stress more rapidly than defeated lizards. We initially examined temporal patterns of neuroendocrine response to restraint stress in lizards of unknown status, and then investigated whether winning males respond more rapidly to this non-social stressor. Size-matched male pairs interacted to establish social status, and then were returned to individual home cages for 3 days. Plasma and brains were collected from non-restrained dominants and subordinates, and from a non-interacting control group. Additional groups of dominants and subordinates underwent 90 s restraint stress, with plasma and brains collected either immediately or 300 s after restraint. In lizards of unknown social status restraint stimulated rapid monoaminergic responses in nucleus accumbens, hippocampus, amygdala, and locus ceruleus, with delayed responses seen in VTA and raphé. Non-restrained dominants and subordinates had lower levels of raphé serotonergic activity and lower hippocampal dopaminergic activity 3 days after interacting, compared to controls. Dominants had higher corticosterone levels, both immediately and 300 s after restraint, than either non-restrained dominants or restrained subordinates. Restraint induced higher raphé serotonergic activity in dominants. However, subordinates also showed rapid responses to restraint; exhibiting lower hippocampal dopamine (DA) levels than non-restrained subordinates. At 300 s after the stress, amygdalar serotonin levels increased in dominants, while subordinates showed higher amygdalar DA levels. These results suggest that stressful aggressive interactions will not only alter basal neurochemical activity, but also influence neuroendocrine responses to non-social stressors according to individual social status.     

Influence of social dominance and female odor on the sperm activity of male mice

In mammals, sperm activity is known to be varied largely according to individuals though physiological reasons have not been clarified yet. In our previous study [Koyama S, Kamimura S. Lowered sperm motility in mice of subordinate social status. Physiol Behav 1999;65:665-669.], we showed that sperm motility was higher in the dominant mice than the subordinate mice, by which it was suggested that social factors could affect sperm activity in mammals. In the present study, we investigated how the observed influence of social dominance would be modified by the existence of females. From 5 to 15 weeks of age, male mice were pair housed and were kept under three different housing conditions: (1) with females; (2) with bedding soiled by females; and (3) control group. The social dominance of the paired males was determined by resident-intruder tests that were carried out from 8 to 15 weeks of age. At the end of 15 weeks of age, sperm activity, weights of organs, level of serum testosterone and corticosterone were determined. It was revealed that sperm density was higher and weight of preputial glands was heavier in dominants than in subordinates when they were kept with females or female bedding. In the subordinates, however, there were no differences among the three housing conditions; that is, there were no female effects on the subordinates. On the other hand, sperm motility was high in the dominants of control group, low in the subordinates, and lower in the dominants that were kept with females. The dominants of the males that were kept with females showed high aggressiveness, and there were negative correlationships to be seen between aggressiveness and sperm motility. It was suggested that: (1) Female odor promotes spermatogenesis of the dominants, but it does not promote that of the subordinates. (2) Sperm motility is more affected by social dominance than by female odor. (3) Excessive aggressiveness has negative influence on sperm motility.     

Endocrine and lymphoproliferative response changes produced by social stress in mice

Daily dyadic resident-intruder encounters and uninterrupted cohabitation in pairs were used to assess the impact of different durations (5 and 15 days) of dominance and subordination experiences on splenic lymphoproliferative responses in male OF1 strain mice. HPA axis activity was assessed by measuring serum corticosterone levels, whereas splenic norepinephrine (NE) content provided a sympathetic activity index. Corticosterone levels in subordinate subjects were generally higher than in their control or dominant counterparts in both treatment paradigms. Corticosterone levels in dominant subjects were lower than in their control counterparts in both. Increasing the duration of treatments generally decreased such titers, especially so in subordinate subjects. No differences were detected in splenic NE content. Animals subjected to social interaction generally showed greater proliferation than their control counterparts. This effect was more pronounced in subordinates than dominants and after longer- rather than short-duration treatments. There was no inverse relation between proliferative responses and the subject's corticosterone levels. While corticosterone may have a general immunomodulating effect, other mediators apparently account for the effects produced by these social stress paradigms on splenic proliferative response.     

Alterations in core body temperature, locomotor activity, and corticosterone following acute and repeated social defeat of male NMRI mice

Repeated social defeat of male NMRI mice, coupled with the stress of continuously living opposite a dominant animal, induces a citalopram-reversible increase in anxiety. The experiments reported in the present paper were performed in an attempt to further validate this paradigm by studying the effects of acute and repeated social defeat on corticosterone and the circadian rhythms of core body temperature and locomotor activity, measured by telemetry. Acute social defeat induced a large (controls: 37.14+/-0.29 degrees C; subordinates: 39.79+/-0.33 degrees C) increase in core body temperature and corticosterone (controls: 30.14+/-2.70 ng/ml; subordinates: 89.62+/-9.25 ng/ml). Repeated social defeat (24 defeats) induced a chronic elevation in core body temperature across 24-h (controls: 36.62+/-0.04 degrees C; subordinates: 37.11+/-0.16 degrees C) in subordinate animals and a very large increase in corticosterone (controls: 28.60+/-1.27 ng/ml; subordinates: 441.52+/-8.86 ng/ml). These results illustrate that the chronic social defeat procedure described in this paper induces a state of chronic stress in the subordinate animals. Further studies are warranted to ascertain if the chronic hyperthermia and increases in corticosterone observed in the subordinate animals could be attenuated by chronic antidepressant treatment, thus further extending the predictive validity of this model.     

Suppression of natural cytotoxic cell activity by social aggressiveness in Tilapia

Our earlier observations revealed that social stress causes drastic effects on different physiological mechanisms and degenerative changes in leucocytes. In this preliminary work, we analyzed the effect of social aggressiveness on functional activities of leucocytes emphasizing (NCC) activity in Tilapia. At 10 hr post stress induction, fish could be differentiated into three categories: 1) dominants; 2) subordinates; and 3) indeterminants. Results of NCC as indicated by 4 hr. 51Cr-release assay, demonstrated a significant suppression in cytotoxic reactivity in the subordinates and indeterminants compared to dominants. This suppression appears to be due to a decrease in the binding capacity of effector cells to YAC-1 target cells as indicated by the decreased number of conjugate forming cells. This binding process is a key event in activating the fish equivalent of NK cells in mammals. Decreased NCC-activity in stressed fish suggests that aberrations in cell mediated immunity result from social aggressiveness.     

Cardiovascular reactivity and neuronal activation to stress in Schlager genetically hypertensive mice

Schlager inbred hypertensive mice (BPH/2J) have been suggested to have high blood pressure (BP) due to an overactive sympathetic nervous system (SNS). The brain nuclei associated with the hypertension are also those involved in the integration of the cardiovascular responses to stress. Therefore, in the present study, we hypothesize that BPH/2J mice likely have a greater response to stress that is associated with greater neuronal activation in the limbic system, hypothalamus and medulla in regions known to regulate sympathetic activity. Male hypertensive BPH/2J and normotensive BPN/3J mice were implanted with telemetry devices and exposed to dirty cage-switch, an acute model of aversive stress. Stress exposure caused a 60% greater pressor response in BPH/2J compared with BPN/3J mice and an increase in activity, by contrast the level of tachycardia was less in BPH/2J mice. Stress-induced cardiovascular responses were also associated with greater neuronal activation, as detected by c-Fos expression, in BPH/2J compared with BPN/3J mice in the medial nucleus of the amygdala (MeAm), dorsomedial hypothalamus (DMH) (P<0.001) and marginally in the rostral ventrolateral medulla (RVLM; P=0.7). These findings suggest that hypertension in the BPH/2J mice is associated with greater sympathetic vasomotor responses to central pathways mediating the arousal responses to acute aversive stress in particular the amygdala, hypothalamus and rostral ventrolateral medulla.     

Social stress in mice: gender differences and effects of estrous cycle and social dominance.

A large discrepancy in the possibility of inducing social stress in the two genders exists. Since generalizations of findings from one sex to the other appear not to be valid, reliable models of social stress in females are needed. We examined the effects of social context in the housing environment, as a possible source of stress, on exploration and anxiety in male and female mice, taking into account the estrous phase for females and the social status for males as additional variables. Mice housed individually or with siblings were tested in a free-exploratory paradigm of anxiety (where test animals have a choice to stay in their home cage or to explore an open field, OF). Individually housed females did not leave their home cage for long periods, explored less the unfamiliar area and displayed higher risk assessment, a behavioral profile suggestive of lower propensity for exploration and higher level of anxiety compared with group-housed females. Individually housed males tended to show an opposite profile. Proestrus mice were less sensitive to the decrease of exploratory propensity induced by individually housing compared to estrus and diestrus mice. Social dominants and social subordinates in sibling groups did not differ in their exploratory responses to the OF. Different housing procedures, as means to provide different social environment, may differentially induce mild social stress in male and female mice.     

Dominance status predicts response to nonsocial forced movement stress in the green anole lizard (Anolis carolinensis)

We used changes in body color and eyespot formation, two somatic indices of stress controlled mainly by catecholamine activity, to compare the reactions of dominant and subordinate male green anole lizards (Anolis carolinensis) to a nonsocial stressor, forced movement. Individual males were pretested by subjecting them to 10 min of forced movement induced by chasing them around their home cage with a slender wooden stick. Stress responses were assayed via changes in body color (progressive darkening from green to brown indicating increasing stress) and expression of a black postorbital eyespot (which appears with increasing catecholaminergic stress responses). Lizards were paired and allowed to form stable dominant/subordinate relationships for 2 weeks. After that period of stable social status, dominants and subordinates were separated and subjected to the same forced-movement stress. There was no difference between experimental groups in the pretest. After assuming positions in the dominance hierarchy, however, dominant males showed reduced somatic indicators of stress and were quicker to recover from the stress. The data suggest that animals that assumed the dominant position decreased their stress response relative to the pretest, while animals that assumed the subordinate position increased their stress response relative to the pretest. The results indicate that dominant social status may have advantages beyond the realm of social interactions by enhancing an individual's ability to tolerate other, nonsocial stressful events.     

Social status and nerve growth factor serum levels after agonistic encounters in mice

Ten repeated daily interactions (20 min each) of the same pairs of isolated male mice produced a clear distinction between attacking (dominant) and defeated (subordinate) animals. The fighting level remained fairly constant over the 10 days. One hr after the end of the 10th session, the increase in serum NGF levels described previously (2) was significantly more marked in subordinate than in dominant mice. The mean level of serum NGF was correlated with the number of fighting episodes, particularly in the case of dominant individuals. Moreover, within-pair differences in NGF values were correlated with differences in locomotor activity between dominants and subordinates; this makes it possible that stimuli other than those produced by fighting per se may be responsible for the increase in circulating NGF. As is well known, the adrenal hypertrophy produced by fighting stress is more marked in subordinate than in dominant mice, while previous work has shown that stress of a nonpsychosocial kind does not elevate serum NGF levels. Therefore, the present data support the hypothesis that NGF release contributes to the modulation of adrenal function in a situation-specific fashion.     

Repeated exposure to social stress has long-term effects on indirect markers of dopaminergic activity in brain regions associated with motivated behavior

The visible burrow system (VBS) is a chronic social stress paradigm in which a dominance hierarchy forms among male rats housed with females. Males in the VBS undergo behavioral and physiological changes thought to be manifestations of chronic social stress. Since it is unclear whether chronic social stress affects motivation and reward behavior, brain areas related to these regions were examined. Long-term effects of a single or repeated VBS exposure on mesolimbic subregions were investigated by exposing rats to the VBS either once (one cycle of VBS housing and recovery) or repeatedly (three cycles). Behavior in the VBS was observed and rats were classified as dominants or subordinates. Subordinates were further sub-classified on the basis of stress hormone (corticosterone) response to an acute stressor (i.e. restraint stress). Normal responders were categorized as stress-responsive subordinates (SRS) and animals with a blunted hypothalamic-pituitary-adrenal axis response were designated as non-responsive subordinates (NRS). Controls males were pair-housed with a single female during VBS periods and alone during recovery. Lowered enkephalin-mRNA levels were observed in the nucleus accumbens (Acb) after single VBS exposure in SRS and repeated VBS exposure both subordinate groups (i.e. SRS + NRS) compared with controls. Decreased dopamine transporter density was detected after single VBS exposure in the dorsolateral caudate putamen (DLCPu) of NRS and after repeated VBS exposure in the Acb of NRS compared with controls. Dopamine D2 receptor density was elevated after single VBS exposure in the Acb of both subordinate groups (SRS + NRS) and after repeated VBS exposure in the DLCPu, dorsomedial CPu, and Acb of NRS compared with controls. No changes in dopamine D1 receptor binding were observed in any group. These results suggest that long-term changes in dopamine activity in mesolimbic structures persist after repeated exposures to chronic social stress and may provide insight into the neurochemical basis of depressive illness and subsequent comorbidity with drug abuse vulnerability.     

Effects of dominance status on conditioned defeat and expression of 5-HT1A and 5-HT2A receptors

Past experience can alter how individuals respond to stressful events. The brain serotonin system is a key factor modulating stress-related behavior and may contribute to individual variation in coping styles. In this study we investigated whether dominant and subordinate hamsters respond differently to social defeat and whether their behavioral responses are associated with changes in 5-HT1A and 5-HT2A receptor immunoreactivity in several limbic brain regions. We paired weight-matched hamsters in daily aggressive encounters for two weeks so that they formed a stable dominance relationship. We also included controls that were exposed to an empty cage each day for two weeks. Twenty-four hours after the final pairing or empty cage exposure, subjects were socially defeated in 3, 5-min encounters with a more aggressive hamster. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains following conditioned defeat testing and performed immunohistochemistry for 5-HT1A and 5-HT2A receptors. We found that dominants showed less submissive and defensive behavior at conditioned defeat testing compared to both subordinates and controls. Additionally, both dominants and subordinates had an increased number of 5-HT1A immunopositive cells in the basolateral amygdala compared to controls. Subordinates also had more 5-HT1A immunopositive cells in the dorsal medial amygdala than did controls. Finally, dominants had fewer 5-HT1A immunopositive cells in the paraventricular nucleus of the hypothalamus compared to controls. Our results indicate that dominant social status results in a blunted conditioned defeat response and a distinct pattern of 5-HT1A receptor expression, which may contribute to resistance to conditioned defeat.     

Cardiac sympathetic activation and parasympathetic withdrawal during psychosocial stress exposure in 6-month-old infants

Infant autonomic reactivity to stress is a potential predictor of later life health complications, but research has not sufficiently examined sympathetic activity, controlled for effects of physical activity and respiration, or studied associations among autonomic adjustments, cardiac activity, and affect in infants. We studied 278 infants during the repeated Still-Face Paradigm, a standardized stressor, while monitoring cardiac activity (ECG) and respiratory pattern (respiratory inductance plethysmography). Video ratings of physical activity and affect were also performed. Respiratory sinus arrhythmia (RSA) and T-wave amplitude (TWA) served as noninvasive indicators of cardiac parasympathetic and sympathetic activity, respectively. Responses were compared between infants who completed two still-face exposures and those who terminated after one exposure due to visible distress. Findings, controlled for physical activity, showed robust reductions in respiration-adjusted RSA and TWA, with more tonic attenuation of TWA. Infants completing only one still-face trial showed more pronounced autonomic changes and less recovery from stress. They also showed elevated minute ventilation, suggesting hyperventilation. Both reductions in adjusted RSA and TWA contributed equally to heart rate changes and were associated with higher negative and lower positive affect. These associations were more robust in the group of distressed infants unable to complete both still-face trials. Thus, cardiac sympathetic activation and parasympathetic withdrawal are part of the infant stress response, beyond associated physical activity and respiration changes. Their association with cardiac chronotropy and affect increases as infants' distress level increases. This excess reactivity to social stress should be examined as a predictor of future cardiovascular disease.     

c-fos expression, behavioural, endocrine and autonomic responses to acute social stress in male rats after chronic restraint: modulation by serotonin

The effects in male rats of serotonin depletion (using the neurotoxin 5,7-dihydroxytryptamine) on the cross-sensitization of an acute social stress (defeat by a larger resident male) by previous repeated restraint stress (10 days, 60 min per day) was studied. Previous restraint increased freezing responses during social defeat in sham-operated rats, but this was not observed in those with depleted serotonin (83% or more in different regions of the brain). In contrast, neither heart rate (tachycardia) nor core temperature responses (hyperthermia) were accentuated in previously restrained rats (i.e. neither showed heterotypical sensitization), and neither adapted to repeated restraint (there is a hypothermic core temperature response during restraint). Corticosterone levels, which did adapt, nevertheless did not show accentuated responses to social defeat in previously restrained rats, though samples could only be taken 60 min after defeat. c-fos expression in the central nucleus of the amygdala 60 min after social defeat was increased by previous restraint. No other areas examined in the hypothalamus (e.g., paraventricular nucleus) or brainstem (e.g., solitary nucleus) showed differences related to previous restraint. Serotonin depletion reduced the expression of c-fos in the frontal cortex, lateral preoptic area, medial amygdala, central gray, medial and dorsal raphe, and locus coeruleus after social stress, but this was not altered by previous restraint. These results show that serotonin depletion has selective effects on the cross-sensitization of responses in previously stressed rats to a heterotypical stressor.     

Quantifying food intake in socially housed monkeys: social status effects on caloric consumption

Obesity results from a number of factors including socio-environmental influences and rodent models show that several different stressors increase the preference for calorically dense foods leading to an obese phenotype. We present here a non-human primate model using socially housed adult female macaques living in long-term stable groups given access to diets of different caloric density. Consumption of a low fat (LFD; 15% of calories from fat) and a high fat diet (HFD; 45% of calories from fat) was quantified by means of a custom-built, automated feeder that dispensed a pellet of food when activated by a radiofrequency chip implanted subcutaneously in the animal's wrist. Socially subordinate females showed indices of chronic psychological stress having reduced glucocorticoid negative feedback and higher frequencies of anxiety-like behavior. Twenty-four hour intakes of both the LFD and HFD were significantly greater in subordinates than dominates, an effect that persisted whether standard monkey chow (13% of calories from fat) was present or absent. Furthermore, although dominants restricted their food intake to daylight, subordinates continued to feed at night. Total caloric intake was significantly correlated with body weight change. Collectively, these results show that food intake can be reliably quantified in non-human primates living in complex social environments and suggest that socially subordinate females consume more calories, suggesting this ethologically relevant model may help understand how psychosocial stress changes food preferences and consumption leading to obesity.     

Long-term effects of social stress on antiviral immunity in pigs

Mixing of unfamiliar pigs is common practice in intensive pig husbandry. Since pigs maintain a dominance hierarchy, mixing often leads to vigorous fighting. Apart from the negative impact that fighting has on welfare, there is evidence that the social stress associated with fighting suppresses immune function. In the present experiment, we investigated the impact of mixing on specific long-term immune responses and protection against challenge infection after vaccination with pseudorabies virus (PRV). Specific pathogen-free (SPF) pigs were mixed pairwise with an unfamiliar same-gender conspecific or left undisturbed with a same-gender littermate at 3 days after vaccination with PRV. Half of the pigs were females (gilts) and half were castrated males (barrows). Mixing increased agonistic behavior to the same degree in gilts and barrows. Cortisol concentrations in saliva and catecholamine excretion in urine were increased in mixed pigs, and these effects were independent of dominance status and gender. Subsequently, the effects of mixing, gender, dominance status and interactions between these factors on immune response parameters were studied. The main result was that mixed barrows showed suppressed immune responses after vaccination and increased clinical symptoms after challenge infection compared to control barrows. Mixed gilts however did not differ from control gilts. It also appeared that mixed dominants were more seriously affected than mixed subordinates were. We conclude that, in some pigs, social stress after mixing suppresses the immune response to a viral vaccine and consequently impairs protection against challenge infection.     

Juvenile stress impairs body temperature regulation and augments anticipatory stress-induced hyperthermia responses in rats

Clinical studies have implicated adolescence as an important and vulnerable period during which traumatic experiences can predispose individuals to anxiety and mood disorders. As such, a stress model in juvenile rats (age 27-29 d) was previously developed to investigate the long-term effects of stress exposure during adolescence on behavior and physiology. This paradigm involves exposing rats to different stressors on consecutive days over a 3-day period. Here, we studied the effects of juvenile stress on long-term core body temperature regulation and acute stress-induced hyperthermia (SIH) responses using telemetry. We found no differences between control and juvenile stress rats in anxiety-related behavior on the elevated plus maze, which we attribute to stress associated with surgical implantation of telemetry devices. This highlights the severe impact of surgical stress on the results of subsequent behavioral measurements. Nonetheless, juvenile stress disrupted the circadian rhythmicity of body temperature and decreased circadian amplitude. It also induced chronic hypothermia during the dark phase of the day, when rats are most active. When subjected to acute social defeat stress as adults, juvenile stress had no impact on the SIH response relative to controls. However, 24 h later, juvenile stress rats displayed an elevated SIH response in anticipation of social defeat when re-exposed to the social defeat environment. Taken together, our findings indicate that juvenile stress can induce long-term alterations in body temperature regulation and heighten the increase in temperature associated with anticipation of social defeat. The outcomes of behavioral measurements in these experiments, however, are severely affected by surgical stress.     

Stress cardiovascular/autonomic interactions in mice

Studies evaluated the role of the autonomic nervous system in the cardiovascular response to stress using radiotelemetric blood pressure (BP) recording coupled with autoregressive spectral analysis. Conscious male C57/BL6 mice with carotid arterial telemetric catheters were exposed to acute episodes of shaker stress before and after administration of cholinergic, beta1-adrenergic and alpha1-adrenergic receptor antagonists. Pulse interval (PI) and systolic arterial pressure (SAP) were analyzed for variance and the low frequency (LF: 0.1-1.0 Hz) and high frequency (HF: 1-5 Hz) spectral components. Stress (5 min) increased BP and heart rate (HR) as well as PI and SAP variability. PI variance increased from 41+/-6 to 75+/-14 ms2 while SAP variance increased from 25+/-5 to 55+/-9 mm Hg2. Autonomic blockade had specific effects on stress-induced changes in PI and SAP and their respective variability. Atropine reduced the tachycardia and abolished the increase in PI variance and its LF component. Data documents that in mice the cholinergic system is fundamental for the maintenance of HR variability. Atropine had no effects on the BP responses, either the increase in SAP or the variance associated with stress. Atenolol blocked the increase in PI and SAP variability induced by stress. Prazosin reduced the tachycardia produced by stress and blocked the increase in PI (only LF) and SAP variability. Using quantitative spectral analysis of telemetrically collected BP data in mice along with pharmacological antagonism, we were able to accurately determine the role of autonomic input in the mediation of the stress response. Data verify the role of sympathetic/parasympathetic balance in stress-induced changes in HR, BP and indices of variance.     

Physiological and health consequences of social status in zebrafish (Danio rerio)

Social status affects access to food, mates and shelter and has consequences for the physiology of individuals and their health status. In the zebrafish (Danio rerio), an emerging model for studies into animal behavior, the possible consequences of social hierarchy to an individual's physiology and health are unknown. To address this, in this species we assessed the effects of social interaction (for periods of 1-5 days) on growth, stress, immune function and reproductive condition. Wide-ranging differences in physiology occurred between the social ranks, some of which were sex-related and time-dependent. In both sexes, dominant fish were larger than subordinates and dominant males had a higher growth rate during the trials. Subordinates had higher plasma cortisol and in males higher telencephalic corticotrophin-releasing hormone, neuropeptide y and glucocorticoid receptor gene expression. Splenic cytokine expression suggested differences in immune status between ranks in both sexes and hematocrit was elevated in subordinate males. In both sexes, dominants and subordinates differed in the expression of genes for various gonadal sex steroid receptors and steroidogenic enzymes and in dominant females the ovary was larger relative to body mass compared with in subordinates. Dominant males had higher plasma 11-ketotestosterone than subordinates and there was an increase in the number of spermatids in their testes over the duration of the study that was not seen in subordinate males. The wide-ranging physiological differences seen between dominant and subordinate zebrafish as a consequence of their social status suggest negative health impacts for subordinates after prolonged durations in those hierarchies.     

Increased vulnerability to stress following opiate exposures: behavioral and autonomic correlates

The authors used rats to study the impact of a history of opiate exposures on behavioral and autonomic responses to restraint stress. Brief restraint (30 min) provoked tachycardia and a pressor response, anxiety (as indexed by social interaction), grooming, and reduced exploration. The pressor response was reduced at 1 day, but not 7 days, after last opiate exposure; tachycardia was unaffected (Experiment 1). Stress-induced anxiety was potentiated 1 and 7 days after last opiate exposure (Experiment 2), and this potentiation was a function of dose (Experiment 3) and duration (Experiment 4) of opiate exposure. The results show that a history of opiate exposures alters vulnerability to stress and has implications for understanding coping, anxiety, and emotionality in former opiate users.