Repeated exposure to social stress alters the development of agonistic behavior in male golden hamsters

In male golden hamsters, exposure to social stress during puberty alters aggressive behavior. Interestingly, agonistic behavior undergoes two major transitions during puberty: a decline in attack frequency and a shift from play fighting to adult-like aggression. Based on previous observations, we developed an approach for characterizing offensive responses as play fighting or adult-like. The present studies had two aims. First, we validated our approach by looking at the development of attack types during puberty. Second, we looked at the effects of repeated social stress on the development of agonistic behavior by repeatedly exposing individuals to aggressive adults during puberty. In the first phase of the study, our results point to three different developmental periods. Initially, animals engage in agonistic behavior though attacks targeted at the face and cheeks. This period lasts from Postnatal Day 20 (P-20) to P-40 (early puberty). This phase corresponding to play fighting is followed by a transitional period characterized by attacks focused on the flanks (from P-40 to P-50, mid-puberty). Afterward, animals perform adult-like aggression characterized by attacks focused on the belly and rear. Our data also show that repeated exposure to aggressive adults has two separate effects on the development of agonistic behavior. Repeated social stress accelerated the onset of adult-like agonistic responses. Furthermore, attack frequency, while decreasing during puberty, remained at a higher level in early adulthood in stressed animals. These results show that repeated exposure to social stress during puberty alters the development of agonistic behavior both qualitatively and quantitatively.     

Stress and the development of agonistic behavior in golden hamsters

Aggressive behavior can be studied as either offensive or defensive responses to a stimulus. The studies discussed in this review are focused on the peripubertal development of offensive aggression in male golden hamsters and its responsiveness to repeated social stress. Quantitative and qualitative changes in offensive responses were analyzed during this period. Quantitative changes in offensive responses were observed as decreased frequency of attacks. Qualitative changes were observed as changes in attack types, as animals reorient their attacks gradually from the face to the lower belly and rump. These developmental changes were altered by repeated exposure to social stress during early puberty. Daily exposure to aggressive adults during early puberty accelerated the qualitative development of offensive responses and the onset of adult-like offensive responses. In contrast, social stress had little effect on the quantitative changes associated with early puberty. However, social stress was associated with higher attack frequency during adulthood. These effects of stress during early puberty contrast with those observed with animals in late puberty. At that time, repeated exposure to aggressive adults inhibits offensive aggression. These data constitute the basis for a new theory on the development of agonistic behavior that includes the following hypotheses. First, it is hypothesized that mid-puberty is marked by a change in responsiveness to repeated social stress. As such, differences in stress responsiveness from social interactions are interpreted as a basic distinction between play fighting and adult aggression. Second, it is also hypothesized that a common neural circuitry mediates the activation of offensive responses during play fighting and adult aggressive interactions.     

Cortisol controls the pubertal development of agonistic behavior in male golden hamsters via type II corticosteroid receptors

In male golden hamsters, agonistic behavior undergoes a pubertal transition from play fighting to adult aggression. Previous studies have shown that this aspect of behavioral development is associated with pubertal increases in glucocorticoids and that daily social stress or injections of a synthetic glucocorticoid accelerate the transition. The goals of this study were to confirm the effects of cortisol on the development of agonistic behavior and to investigate the role of type II corticosteroid receptors in this process. First, animals treated with cortisol during early puberty [from postnatal days 31 (P-31) to P-36] showed an accelerated transition from play fighting to adult aggression. In a second experiment, the behavioral effects of cortisol were blocked by a co-treatment with a type II corticosteroid receptor antagonist. These findings are the first to show a facilitating role for type II corticosteroid receptors in the pubertal development of a social behavior. As such, these findings provide new insights into the neuroendocrine mechanisms controlling behavioral development during puberty.     

Gonadal hormones modulate the display of submissive behavior in socially defeated female Syrian hamsters

There are striking differences in the behavioral response to social defeat between male and female Syrian hamsters. Whereas males exhibit a prolonged behavioral response to defeat (i.e., conditioned defeat), many females remain aggressive or show only a transient submissive response following defeat. The current study tested the hypothesis that sex steroids underlie this differential behavioral responsivity to social defeat. Female hamsters were ovariectomized and implanted with Silastic capsules containing estradiol (E(2)), testosterone (T), progesterone (P), dihydrotestosterone (DHT), or a blank capsule (no hormone replacement). After a 3-week recovery period, each subject was placed inside the home cage of a larger, more aggressive female for four 5-min defeat trials. The following day, each animal was tested for conditioned defeat by testing it in its own home cage in the presence of a smaller, non-aggressive intruder. Submissive, aggressive, social, and nonsocial behaviors were subsequently scored. Hamsters receiving E(2) or T displayed significantly lower levels of submissive behavior than did animals receiving P, DHT, or no hormone replacement. There were no significant differences in aggressive behavior among groups. These data suggest that gonadal hormones can influence submissive behavior in female hamsters. Collectively, these results suggest that the sex differences observed in conditioned defeat may, in part, be explained by sex differences in circulating gonadal hormones.     

Risk assessment and avoidance in juvenile golden hamsters exposed to repeated stress

Juvenile hamsters are typically less vulnerable to social subjugation than adults, although they will avoid aggressive individuals in some situations. The purpose of this study was to determine the extent to which social subjugation stimulates fear- or anxiety-like behavior in juvenile hamsters in both social and non-social contexts. Social context testing was conducted in a Y-maze while the non-social context apparatus consisted of an open field arena and a lat-maze. In the Y-maze, subjects were exposed to an unfamiliar aggressive adult hamster. Compared with non-subjugated controls, subjugated juveniles spent significantly more time in the area furthest from the aggressive adult stimulus. In addition, socially stressed animals were more likely to avoid the arm of the maze containing the social stimulus. When they did walk in the arm containing the social stimulus, subjugated individuals were more likely to ambulate slowly. Subjugated hamsters also performed fewer olfactory investigations in the proximity of the unfamiliar aggressive individual. Despite these behavioral differences detected between groups during testing in a social context, we observed no differences between groups in the open field and lat-maze. This suggests that the effects of subjugation observed in the Y-maze are specific to exposure to a social context and that social subjugation in juvenile hamsters does not result in a generalized state of fear. Instead, subjugated juveniles learned to avoid adult males and were otherwise behaviorally similar to non-subjugated controls.     

Conditioned defeat in male and female Syrian hamsters

A brief exposure to social defeat in male Syrian hamsters (Mesocricetus auratus) leads to profound changes in the subsequent agonistic behavior exhibited by the defeated animals. Following defeat in the home cage of an aggressive conspecific, male hamsters will subsequently fail to defend their home territory even if the intruder is a smaller, nonaggressive male. This phenomenon has been called conditioned defeat. In Experiment 1, we examined the duration of conditioned defeat by repeatedly testing (every 3-5 days) defeated hamsters with a nonaggressive intruder. We found that conditioned defeat occurs in all defeated male hamsters and persists for a prolonged period of time (at least 33 days) in the majority of male hamsters tested despite the fact that these animals are never attacked by the nonaggressive intruders. In Experiment 2, we examined whether conditioned defeat could be induced in female Syrian hamsters. While conditioned defeat occurred in some females, they displayed only low levels of submissive/defensive behavior and, in contrast to males, the conditioned defeat response did not persist beyond the first test. These results suggest that in male hamsters conditioned defeat is a profound, persistent behavioral change characterized by a total absence of territorial aggression and by the frequent display of submissive and defensive behaviors. Conversely, social defeat in female hamsters does not appear to induce long-term behavioral changes. Finally, in Experiment 3, we determined that plasma adrenocorticotropin-like immunoreactivity increases in females following social defeat in a manner similar to that seen in males, suggesting that the disparate behavioral reactions of males and females are not due to sex differences in the release of, or response to, plasma adrenocorticotropin.     

Prenatal stress differentially affects habituation of corticosterone responses to repeated stress in adult male and female rats

Environmental factors operating early in life have long-lasting and important consequences for the mental and physical health of the adult organism. In particular, prenatal exposure to stress represents one category of adverse early environmental events that are associated with development of depression and schizophrenia in adulthood. In the present studies, we examined whether prenatal stress alters the habituation of hypothalamic-pituitary-adrenal (HPA) activity that occurs with repeated stress exposure in adulthood. We compared corticosterone responses to the first vs. the eighth restraint, with lower responses to the eighth vs. the first considered evidence of habituation. In males, prenatal stress prevented the habituation of corticosterone responses to repeated restraint that was observed in non-prenatally stressed rats. Limited evidence of habituation was seen in either group of females and prenatally stressed females did not exhibit the enhanced corticosterone response during recovery from the eighth restraint that was seen in non-prenatally stressed females. Together, these results suggest a sex-specific interaction between prenatal stress and adult chronic stress on HPA activity.     

Pre-pubertal gonadectomy and the social consequences of acute ethanol in adolescent male and female rats

It has previously been shown that pre-pubertal or adult gonadectomy (GX) increases ethanol intake in male rats. This study examined whether this sex-selective increase reflects a GX-induced maintenance in males of more adolescent-typical responsiveness to ethanol characterized by enhanced sensitivity to positive (e.g., socially facilitating) and a decreased sensitivity to adverse (e.g., socially inhibitory) effects of ethanol. Male and female Sprague-Dawley rats were pre-pubertally GX, sham (SH)-operated, or non-manipulated (NM) at postnatal day (P) 25. During the late adolescent transition into adulthood (P48 — baseline day), rats were given a saline injection, placed alone into a familiar test apparatus for 30 min and then exposed for 10 min to an unfamiliar partner of the same age and sex. On the following day (P49), similar testing occurred after administration of 0.5, 0.75, 1.0 or 1.25 g/kg ethanol. At baseline, GX males and females displayed higher levels of social activity (especially adolescent-typical play and contact behavior) than SH and NM animals, with GX females displaying greater social activity than GX males. Neither males nor females demonstrated social facilitation at lower ethanol doses, regardless of hormonal status. Whereas the social inhibitory effects of higher doses of ethanol were similar across groups among females, SH males were less sensitive than both GX and NM males to ethanol-induced social inhibition. These results suggest that enhanced ethanol intake in GX males is not related to alterations in sensitivity to ethanol's social inhibitory effects. GX, however, results in retention of adolescent-typical social behaviors, with older GX adolescent rats resembling early adolescents in exhibiting elevated social activity—particularly play and contact behavior.     

Androgenic anabolic steroid exposure during adolescence: Ramifications for brain development and behavior

This article is part of a Special Issue “Puberty and Adolescence”.     

Pubertal maturation and time of day differentially affect behavioral and neuroendocrine responses following an acute stressor

Puberty markedly influences stress responsiveness such that prepubertal animals show a more protracted corticosterone (CORT) and progesterone response following acute stress compared to adults. In both adult and juvenile rats, circadian time modulates adrenocortical steroids with basal CORT and progesterone levels rising prior to the onset of the dark phase of the light-dark cycle (i.e., active period). How time of day affects the pubertal difference in stress responsiveness and if the behaviors of prepubertal and adult animals are differentially affected by stress and time of testing remain unknown. Thus, we exposed group housed (3 per cage) prepubertal (28d) and adult (77d) male rats to 30 min of restraint in either the early portion of the behaviorally inactive, light (circadian nadir of CORT and progesterone) or behaviorally active, dark (circadian peak) phase of their light-dark cycle and measured ACTH, CORT, progesterone, and home cage behavior before and after the stressor. We found that the extended hormonal stress response demonstrated by prepubertal males occurred at both times of day. However, differences in post-stress behavior were dependent on time of testing. Specifically, although pre- and post-stress behaviors were similarly affected by the stressor in the light phase in prepubertal and adult males, during the dark phase, stress suppressed play behavior in the prepubertal males, and increased their time spent resting together (huddling), while these behaviors were unaffected by stress in the adults. These data indicate that pubertal development and time of day interact to modulate post-stress behavior and demonstrate a dissociation between post-stress hormonal and behavioral responses.     

Photoperiodic regulation of adrenal hormone secretion and aggression in female Syrian hamsters

Seasonal changes in the length of the daily photoperiod induce significant changes in social behavior. Hamsters housed in winter-like short photoperiods (SP) can express significantly higher levels of aggression than hamsters housed in long photoperiods (LP) that mimic summer. The mechanisms responsible for increasing aggressiveness in SP-exposed female hamsters are not well understood but may involve seasonal changes in the endocrine system. In experiment 1, the effects of SP exposure on the circulating levels of three adrenal hormones were determined. Short photoperiod exposure was found to significantly depress the circulating levels of cortisol and the adrenal androgen dehydropiandrosterone (DHEA) but significantly increased the circulating levels of the sulfated form of DHEA, DHEAS. Experiment 2 examined the effects of gonadal hormones on several different measures of aggression including its intensity in females housed in both long and short photoperiod. Exposure to SP resulted in high levels of aggression regardless of the endocrine state of the animal or the measure used to quantify aggression. In contrast, administration of estradiol to hamsters housed in LP significantly reduced aggression. The data of the present study support the hypothesis that SP-housed females are more aggressive than LP-housed females because SP exposure renders females insensitive to the aggression-reducing effects of ovarian hormones.     

Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates

This article is part of a Special Issue “Puberty and Adolescence”.     

Sex and estrous cycle differences in the display of conditioned defeat in Syrian hamsters

We have reported that there is a sex difference in the behavioral response to social defeat in hamsters. While previously defeated male hamsters fail to display normal territorial aggression and instead produce submissive/defensive behavior, a phenomenon that we have termed conditioned defeat (CD), only a small portion of previously defeated females exhibit CD. In Experiment 1, we tested the hypothesis that CD varies over the estrous cycle and found that previously defeated female hamsters tested on diestrus 2 and proestrus were more likely to exhibit CD than were females tested on diestrus 1 and estrus. In Experiment 2, we found that regardless of hormonal status, non-defeated females displayed normal territorial aggression, indicating that the behavioral changes observed in Experiment 1 were not due to a cyclic variation in submissive behavior independent of a previous defeat encounter. In Experiment 3, we found that females tested 4 days after defeat responded similarly to those tested 1 day after defeat suggesting that the hormonal status of females on the day of testing is a more important determinant of the behavioral response to defeat than is the hormonal status on the day of defeat training. Finally, in Experiment 4, we monitored anxiety-like behaviors in diestrous 1 and proestrous females in an open field arena and found that there was no effect of cycle on any of the observed behavioral measures, suggesting that the observed differences in CD are not the result of differences in generalized anxiety-like behaviors across the estrous cycle.     

Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone used by over half a million adolescents in the United States for their tissue-building potency and performance-enhancing effects. AAS also affect behavior, including reports of heightened aggression and changes in sexual libido. The expression of sexual and aggressive behaviors is a function of complex interactions among hormones, social context, and the brain, which is extensively remodeled during adolescence. Thus, AAS may have different consequences on behavior during adolescence and adulthood. Using a rodent model, these studies directly compared the effects of AAS on the expression of male sexual and aggressive behaviors in adolescents and adults. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or in adulthood (63-77 days of age). The day after the last injection, males were tested for either sexual behavior with a receptive female or agonistic behavior with a male intruder. Adolescent males treated with AAS showed significant increases in sexual and aggressive behaviors relative to vehicle-treated adolescents. In contrast, AAS-treated adults showed significantly lower levels of sexual behavior compared with vehicle-treated adults and did not show heightened aggression. Thus, adolescents, but not adults, displayed significantly higher behavioral responses to AAS, suggesting that the still-developing adolescent brain is more vulnerable than the adult brain to the adverse consequences of AAS on the nervous system and behavior.     

Neuroendocrine and neurotransmitter correlates in children with antisocial behavior

When antisocial behavior becomes a persistent pattern that affects diverse domains of children's functioning, psychiatrists refer to oppositional defiant disorder (ODD) or conduct disorder (CD). The term disruptive behavior disorder (DBD) covers both ODD and CD. Research shows that in the absence of effective interventions, the prognosis for DBD children is relatively unfavorable: their disorder can extend into adolescence, manifest itself in delinquency, and convert into other psychiatric symptoms, such as addiction or personality disorders. Although environmental factors have traditionally attracted most attention in explaining the origin and persistence of DBDs, it is important not to overlook the vulnerability of the child in the development of antisocial behavior. Relatively few studies have been conducted on the neurobiological factors involved in the development of DBDs in children. In this paper, we explain how problems in hypothalamic-pituitary-adrenal (HPA) axis and serotonergic system functioning could be important factors in the behavioral problems of DBD children. Low fear of punishment and physiological underactivity may predispose antisocial individuals to seek out stimulation or take risks and may explain poor (social) conditioning and socialization. Findings consistent with this hypothesis are presented. Finally, we explain how stress in general, and adverse early life experiences in particular, could have an impact on the development of the HPA and serotonergic systems. An investigation of the neurobiological factors involved in antisocial behavior disorder might ultimately guide the development of new forms of intervention.     

Dynamics of social and energetic stress in wild female chimpanzees

Stress hormone measurements can reinforce and refine hypotheses about the costs of particular contexts or behaviors in wild animals. For social species, this is complicated because potential stressors may come from the physical environment, social environment, or some combination of both, while the stress response itself is generalized. Here, we present a multivariate examination of urinary cortisol dynamics over 6 years in the lives of wild female chimpanzees in the Kanyawara community of Kibale National Park, Uganda. We hypothesized that chimpanzee socioecology provides strong indications of both energetic and social stress to females, but that the salience of these stressors might vary over a female's life history in accordance with their changing reproductive costs and social interactions. Using linear mixed models, we found that urinary cortisol levels increased significantly with age but were also elevated in young immigrants to the community. Across reproductive states, cycling, non-estrous females had relatively low cortisol compared to lactating, estrous, or pregnant females. Aggression from males led to higher cortisol levels among estrous females, frequent targets of aggressive sexual coercion. In contrast, energetic stress was most salient to lactating females, who experienced higher cortisol during months of low fruit consumption. Low dominance rank was associated with increased cortisol, particularly during the energetically demanding period of lactation. The effects of female conflict were felt widely, even among those who were the primary aggressors, providing further evidence that long-term resource competition, while apparently muted, exerts a far-reaching impact on the lives of chimpanzee females.     

Sex differences and developmental effects of oxytocin on aggression and social behavior in prairie voles (Microtus ochrogaster)

Various hormones, including sex steroids and neuropeptides, have been implicated in aggression. In this study we examined (1) sex differences in intrasexual aggression in na?ve prairie voles; (2) the effects of developmental manipulations of oxytocin on intrasexual aggression; and (3) changes in patterns of intrasexual aggression after brief exposure to an animal of the opposite sex. Within 24 h of birth, infants were randomly assigned to receive either an injection of oxytocin (OT) or oxytocin antagonist (OTA) or to one of two control (CTL) groups receiving either isotonic saline or handling without injection. As adults, animals were tested twice in a neutral arena; before (Test 1) and 24 h after (Test 2) a 4-h exposure to an animal of the opposite sex. In Test 1, CTL males were more likely to show aggressive and less likely to show social behavior than CTL females. No significant treatment differences were observed within either sex in Test 1. In Test 2, after brief exposure to a male, females treated with OT became more aggressive and less social than OTA or CTL females. Male aggressive behavior did not change after exposure to a female. An increase in aggression and decline in social behavior toward other females, seen here in OT-treated females, is typically observed only following several days of female-male cohabitation. These findings demonstrate a sex difference in intrasexual aggression and suggest that neonatal exposure to OT may facilitate the onset of the mate-guarding component of pair bonding in female prairie voles.     

Long-term behavioral and neuroendocrine alterations following chronic social stress in mice: implications for stress-related disorders

The period of adolescence is characterized by a high vulnerability to stress and trauma, which might result in long-lasting consequences and an increased risk to develop psychiatric disorders. Using a recently developed mouse model for chronic social stress during adolescence, we studied persistent neuroendocrine and behavioral effects of chronic social stress obtained 12 months after cessation of the stressor. As a reference, we investigated immediate effects of chronic stress exposure obtained at the end of the chronic stress period. Immediately after the 7 week chronic stress period stressed animals show significantly increased adrenal weights, decreased thymus weight, increased basal corticosterone secretion and a flattened circadian rhythm. Furthermore, stressed animals display an increased anxiety-like behavior in the elevated plus maze and the novelty-induced suppression of feeding test. Hippocampal mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) mRNA levels were significantly decreased. To investigate persistent consequences of this early stressful experience, the same parameters were assessed in aged mice 12 months after the cessation of the stressor. Interestingly, we still found differences between formerly stressed and control mice in important stress-related parameters. MR expression levels were significantly lower in stressed animals, suggesting lasting, possibly epigenetic alterations in gene expression regulation. Furthermore, we observed long-term behavioral alterations in animals stressed during adolescence. Thus, we could demonstrate that chronic stress exposure during a crucial developmental time period results in long-term, persistent effects on physiological and behavioral parameters throughout life, which may contribute to an enhanced vulnerability to stress-induced diseases.     

Sex differences and similarities in the neuroendocrine regulation of social behavior in an African cichlid fish

An individual's position in a social hierarchy profoundly affects behavior and physiology through interactions with community members, yet little is known about how the brain contributes to status differences between and within the social states or sexes. We aimed to determine sex-specific attributes of social status by comparing circulating sex steroid hormones and neural gene expression of sex steroid receptors in dominant and subordinate male and female Astatotilapia burtoni, a highly social African cichlid fish. We found that testosterone and 17β-estradiol levels are higher in males regardless of status and dominant individuals regardless of sex. Progesterone was found to be higher in dominant individuals regardless of sex. Based on pharmacological manipulations in males and females, progesterone appears to be a common mechanism for promoting courtship in dominant individuals. We also examined expression of androgen receptors, estrogen receptor α, and the progesterone receptor in five brain regions that are important for social behavior. Most of the differences in brain sex steroid receptor expression were due to sex rather than status. Our results suggest that the parvocellular preoptic area is a core region for mediating sex differences through androgen and estrogen receptor expression, whereas the progesterone receptor may mediate sex and status behaviors in the putative homologs of the nucleus accumbens and ventromedial hypothalamus. Overall our results suggest sex differences and similarities in the regulation of social dominance by gonadal hormones and their receptors in the brain.     

Sex differences in the behaviour of immature captive lowland gorillas

Studies of the behaviour of 26 (12 males and 14 females) captive infant and juvenile lowland gorillas showed clear sex differences. Females showed greater interest in young infants and were more active in nest building as well as in solitary and social grooming. Males were more active in locomotive, dominance, and aggressive behaviour and in social play. Hand-rearing further increased aggression. Males were more aggressive when they lived with only one partner, and they rose in rank even above older females, a pattern that has not been observed in naturally reared gorillas.