An acute social defeat stressor in early puberty increases susceptibility to social defeat in adulthood

Syrian hamsters readily display territorial aggression. If they lose even a single agonistic encounter, however, hamsters show striking reductions in aggressive behavior and increases in submissive behavior, a distinct behavioral change that we have previously termed conditioned defeat. This acute social defeat stressor is primarily psychological and is effective in both males and females. Therefore, we maintain that this procedure presents an ideal model for studying behavioral and physiological responses to social stress. Here, we demonstrate that social avoidance following social defeat is a particularly useful dependent measure because of its sensitivity and stability between sexes and across the estrous cycle. In addition, we demonstrate that peripubertal hamsters exposed to a single, 15 min social defeat exhibit significantly more social avoidance 24 h later when compared with no-defeat controls. Later, defeated and non-defeated hamsters display similar agonistic behavior in adulthood indicating that the peripubertal defeat does not alter adult territorial aggression. After experiencing an additional social defeat in adulthood, however, the hamsters that experienced the pubertal defeat respond to the adult defeat with increased social avoidance when compared with hamsters that were defeated only in adulthood and with no-defeat controls. These data are the first to show that a single social defeat in puberty increases susceptibility to later social defeat in both males and females.     

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.     

Gonadal hormones modulate the display of conditioned defeat in male Syrian hamsters

It has been widely reported that gonadal hormones influence the display of aggression in Syrian hamsters; conversely, much less is known about whether gonadal hormones modulate submissive/defensive behaviors in these animals. Following social defeat, male hamsters no longer display normal territorial aggression but instead display submissive/defensive behavior in the presence of a smaller opponent, a phenomenon we have termed conditioned defeat (CD). The purpose of the present study was to examine the effect of gonadal hormones on the display of CD in male hamsters. In Experiment 1, males were castrated or sham-operated. The castrated males were significantly more submissive following social defeat relative to their intact counterparts. The increased submissive behavior in the castrated males during CD testing was particularly surprising, given the fact that they were attacked significantly less during CD training. In Experiment 2a, males were castrated and given hormone replacement. Castrated males treated with testosterone or dihydrotestosterone displayed significantly less submissive behavior following social defeat than did those treated with cholesterol or estradiol. Finally, in Experiment 2b, there was no effect of hormone replacement on aggressive behavior in non-defeated hamsters suggesting that the decrease in submissive behavior in males treated with dihydrotestosterone or testosterone is specific to being previously defeated. Taken together the data indicate that the presence of androgens reduces the display of submission in defeated male hamsters. More importantly, these findings suggest that androgens may have a protective effect against the development of depression-like or anxiety-like behaviors following exposure to an ethologically relevant stressor.     

Aggression in the female golden hamster: effects of reproductive state and social isolation

To gain information on possible hormonal correlates, the aggressive behavior of intact female hamsters towards males was observed at various times during the estrous cycle, pseudopregnancy, pregnancy, and lactation. For methodological information, estrous cycle females also were tested after varying periods of social isolation. It was found that pregnant and especially lactating hamsters were more aggressive than pseudopregnant or estrous cycling females. Comparisons of days within each reproductive condition showed that aggression tended to be higher on certain days: the day preceding behavioral estrus of the estrous cycle, Day 10 of pregnancy, and the first 5 days of lactation. Except for pseudopregnancy, sexual behavior unaccompanied by aggression occurred at some time during all reproductive conditions, and both sexual behavior and aggression were found to occur together on Day 10 of pregnancy and Day 1 of lactation. The changes in aggressive behavior associated with reproductive states were attributed to increased male interest, inhibition by ovarian hormones, and facilitation by prolactin. Increasing periods of social isolation also were found to be associated with increased aggression. It was suggested that this effect, too. might have been due to increased prolactin levels.     

Repeated agonistic encounters in hamsters modulate AVP V1a receptor binding

Arginine vasopressin (AVP) regulates aggression in male Syrian hamsters. In this study, we used radioligand receptor autoradiography to examine whether changes in agonistic behavior following acute and repeated social defeat are accompanied by changes in AVP V1a receptor binding. Social defeat produced high levels of submissive behavior and a loss of territorial aggression when hamsters were subsequently tested with a novel intruder, and repeated agonistic encounters produced similar behavioral changes in subordinates. AVP V1a receptor binding was not reduced by acute social defeat but was affected by repeated agonistic encounters. Dominants had significantly more AVP V1a receptor binding in lateral portions of the ventromedial hypothalamus (VMHL) than did their subordinate opponents, but subordinates were no different from controls. In contrast, receptor binding did not differ in most other brain regions examined. The changes in receptor binding appear to be independent of testosterone levels, as testosterone levels did not differ among dominants, subordinates, and controls. Our results suggest that changes in AVP V1a receptors do not account for the changes in agonistic behavior produced by acute social defeat but AVP V1a binding in the VMHL correlates with, and may modulate, the behavioral changes that occur following repeated experiences of victory.     

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.     

Short-day increases in aggression are independent of circulating gonadal steroids in female Siberian hamsters (Phodopus sungorus)

Among the suite of adaptations displayed by seasonally-breeding rodents, individuals of most species display reproductive regression and concomitant decreases in gonadal steroids during the winter. In addition, some species display increased aggression in short "winter-like" days compared with long "summer-like" day lengths. For example, male Syrian and Siberian hamsters held in short days express heightened levels of aggression that are independent of gonadal steroids. Virtually nothing is known, however, regarding seasonal aggression in female Siberian hamsters (Phodopus sungorus). Studies were undertaken to determine female levels of aggression in long and short days as well as the role of gonadal steroids in mediating this behavior. In Experiment 1, females were housed in long or short days for 10 weeks and resident-intruder aggression was assessed. Prior to testing, estrous cycle stages were determined by vaginal cytology and females were tested during both Diestrus I and Proestrus. In Experiment 2, hormone levels were experimentally manipulated; long-day females were ovariectomized (OVx) or given sham surgeries whereas short-day females were implanted with capsules containing 17beta-estradiol (E(2)) or Progesterone (P). In Experiment 3, both long- and short-day females were ovariectomized and implanted with either an exogenous E(2) or blank capsule, or given a sham surgery. Short-day hamsters displayed increased aggression relative to long-day females. Aggression was not affected by estrous stage. There was no difference in aggression between long-day OVx and sham animals. Furthermore, neither exogenous E(2) nor P had any significant effect on aggression. These results support previous findings of increased non-breeding aggression and suggest that short-day aggression is not likely mediated by circulating levels of gonadal steroids. These results also suggest that the endocrine regulation of seasonal aggression may be similar between the sexes.     

Characterization of behavioural responses in different test contexts after a single social defeat in male golden hamsters (Mesocricetus auratus)

The objective of the present study was to characterize behavioural responses of male hamsters in each of three test contexts after they had experienced either a single social defeat or a neutral encounter. In experiment 1, hamsters were observed in a familiar social context (i.e., their home cages), and defeated males displayed different amounts of time and submissive behaviours towards a known opponent than a novel intruder, whereas males in the neutral-encounter groups did not show such differences. In experiment 2, in an unfamiliar social context (i.e., a Y-maze), defeated males generated submissive behaviours and fear memory towards a known opponent that they re-encountered 5-min and 24-h after the defeat. The formation of long-term memory was interrupted by an injection of anisomycin (210 mg/kg). In experiment 3, in a non-social, anxiogenic context, hamsters that had previously had different social experiences did not demonstrate additional anxiety in an elevated plus-maze, with the exception of males that had previously experienced repeated social defeats. Our data suggested that hamsters’ behavioural changes following defeat are context-dependent and stimulus-specific. The experience of a single social defeat is sufficient to regenerate submissive behaviours and fear memory when reencountering a known opponent.     

Effects of repeated aggressive encounters on approach to a female and plasma testosterone in male mice

Effects of repeated experience of aggression accompanied by social victories or social defeat in 10 daily agonistic confrontations on testosterone levels in and the behavioral response of CBA/Lac male mice exposed to a receptive female from behind a perforated transparent partition have been examined. Testosterone levels were not changed significantly in the mice that had consistently been victorious over 10 days (winners) or in the mice that had consistently been defeated over 10 days (losers). Losers and controls (mice that had been caged individually for 5 days) responded with increased levels of behavioral activity near the partition and elevated testosterone. Winners showed a significantly poorer behavioral and hormonal response. It is concluded that the repeated display of aggression by male mice led to a reduction in both their behavioral and neuroendocrine responses to an estrous female.     

Adrenal hormones mediate melatonin-induced increases in aggression in male Siberian hamsters (Phodopus sungorus)

Among the suite of seasonal adaptations displayed by nontropical rodents, some species demonstrate increased territorial aggression in short compared with long day lengths despite basal levels of testosterone. The precise physiological mechanisms mediating seasonal changes in aggression, however, remain largely unknown. The goal of the present study was to examine the role of melatonin, as well as adrenal hormones, in the regulation of seasonal aggression in male Siberian hamsters (Phodopus sungorus). In Experiment 1, male Siberian hamsters received either daily (s.c.) injections of melatonin (15 microg/day) or saline 2 h before lights out for 10 consecutive days. In Experiment 2, hamsters received adrenal demedullations (ADMEDx), whereas in Experiment 3 animals received adrenalectomies (ADx); control animals in both experiments received sham surgeries. Animals in both experiments subsequently received daily injections of melatonin or vehicle as in Experiment 1. Animals in all experiments were tested using a resident-intruder model of aggression. In Experiment 1, exogenous melatonin treatment increased aggression compared with control hamsters. In Experiment 2, ADMEDx had no effect on melatonin-induced aggression. In Experiment 3, the melatonin-induced increase in aggression was significantly attenuated by ADx. Collectively, the results of the present study demonstrate that short day-like patterns of melatonin increase aggression in male Siberian hamsters and suggest that increased aggression is due, in part, to changes in adrenocortical steroids.     

Sexual behavior of the female porcupine Hystrix africaeaustralis

Porcupines are sexually active throughout the estrous cycle, and sexual behavior is not affected by the reproductive status and hormonal milieu of females. Increased female-male interactions during estrus are the only indications of behavioral changes during estrus. The lack of aggression shown by females to known males as opposed to aggression shown to strange males, the greater interest shown by males toward certain females, and the superior breeding success of these females suggest a pair-bonding mating system. Limited changes in female receptivity throughout the cycle might be of importance in maintaining the pair-bond.     

Behavioral and neuroendocrine consequences of social subjugation across adolescence and adulthood

BACKGROUND: Social subjugation is a very significant and natural stressor in the animal kingdom. Adult animals defeated and subjugated during establishment of dominance hierarchies or territorial encounters can be highly submissive in future agonistic interactions. While much is know about the biological and behavioral consequences of winning and losing fights in adulthood, little is known about adolescence; a developmental period noted for impulsivity and heightened agonistic behavior. The present studies were undertaken to determine if the behavioral and neuroendocrine consequences of social subjugation are comparable in adolescent versus adult Syrian golden hamsters (Mesocricetus auratus). Male siblings were studied from adolescence into adulthood following exposure to counterbalanced episodes of either a benign stressor, i.e., isolation in a novel cage, or the more severe stressor of social subjugation. RESULTS: As adults, hamsters with a history of social subjugation in adolescence show high levels of aggression toward intruders as compared to siblings subjugated in adulthood. Sibling controls subjugated in adulthood are highly submissive with little or no aggressive behavior. However, when subjugated in adulthood, hamsters with the earlier history of subjugation are no different than their sibling controls, i.e., adult subjugation promotes submissive behavior. Sexual motivation is high in adult hamsters with adolescent subjugation and testosterone levels remained stable over adulthood. In contrast, sibling controls subjugated in adulthood show lower levels of sexual motivation and reduced levels of testosterone. Release of cortisol during agonistic encounters is blunted in animals subjugated in adolescence but not adulthood. Measures of anxiety are reduced in hamsters with adolescent subjugation as compared to their sibling controls. CONCLUSION: These data demonstrate a pronounced difference in behavior and neuroendocrinology between adolescent and adult hamsters in their response to social subjugation and suggest adolescence is a resilient period in development.     

Aggressive behaviour in rats: Effects of winning or losing on subsequent aggressive interactions

CPB-WE rats (WEzobs) tested for aggression against Tryon Maze Dull rats (S3s) were highly consistently defeated. In contrast, when tested against Wistars, these WEzobs become dominant. On the basis of these findings an experimental procedure was used in which the changes in agonistic responses as the result of experience of victory or defeat could be established. In addition, the effect of winning or losing was studied in subsequent encounters of winners and defeated WEzobs. The result of this experiment clearly indicate that a significant and relatively permanent behavioural inhibition develops in the defeated WEzobs which show less social initiative and aggression than the winners. The behavioural inhibition which is also seen in the spatial orientation of the animals within the test arena was still present after a 14 day interval. Significant loss of body weight was found in the losing animals.     

Enhancement and suppression of ultradian and circadian rhythms across the female hamster reproductive cycle

The impact of ovarian hormones on hamster ultradian rhythms (URs) is unknown. We concurrently monitored URs and circadian rhythms (CRs) of home cage locomotor activity during the estrous cycle, pregnancy, and lactation of Syrian hamsters. URs with a mean period of 4-5 h were evident during the dark phase in more than 90% of females on days 1 and 2 of the estrous cycle but were significantly less prevalent on cycle days 3 and 4. The period of the UR did not vary as a function of estrous cycle stage, but at all stages, the UR period was longer in the dark than the light phase. The UR acrophase occurred significantly earlier on cycle day 4 than on days 1 and 2, and UR robustness and amplitude were reduced on days 3 and 4. Robustness, mesor, and amplitude of CRs were greater during cycle days 3 and 4; timing of the CR acrophase was delayed on day 4 relative to all other cycle days. Effects of the estrous cycle on URs were evident only during the dark phase. The proportion of hamsters displaying dark phase URs increased significantly during early and late gestation and decreased during lactation. Pregnancy significantly increased UR complexity, robustness, and amplitude. The emergence of URs over gestation was paralleled by decrements in the robustness and amplitude of CRs, which also were absent in a significant proportion of dams during lactation but re-emerged at weaning of litters. The changing endocrine profile of the estrous cycle, hormonal dynamics of pregnancy and lactation, and nursing demands placed on dams are each associated with alterations in the expression of ultradian and circadian locomotor rhythms. Diminution of CRs and augmentation of URs may afford greater behavioral flexibility during life stages when interactions with mates and offspring are less predictable.     

Photoperiodic modulation of sexual and aggressive behavior in female golden hamsters (Mesocricetus auratus): role of the pineal gland

Pinealectomized female hamsters (Mesocricetus auratus) housed in a short-day photoperiod were ovariectomized and tested for hormone-induced sexual receptivity in order to investigate the role of the pineal gland in the control of behavioral sensitivity to exogenous ovarian steroid hormones (Experiment 1). Behavioral sensitivity to hormones was further investigated in females maintained in a long-day photoperiod and rendered acyclic by daily administration of exogenous melatonin (Experiment 2). Female aggressive behavior was also monitored in all tests. Pinealectomy did not affect the reduced behavioral sensitivity to exogenous estrogen (E) induced by short days. These animals were also partially refractory to the effects of E when combined with low doses of progesterone. In addition, although melatonin administration mimicked the effects of short days on estrous cyclicity, the expression of hormone-dependent behaviors in these animals resembled the pattern displayed by control animals kept in long days. Thus, these findings suggest that the pineal gland plays a negligible role in the photoperiodic modulation of hormone-dependent sociosexual behaviors in female hamsters.     

Using fecal hormonal and behavioral analyses to evaluate the introduction of two sable antelope at Lincoln Park Zoo

Introductions of sable antelope (Hippotragus niger) can be difficult due to the potential ensuing aggression compounded by their large horns. The goal was to use hormonal assays and behavioral analyses to evaluate the success of an introduction of 2 adult females at Lincoln Park Zoo. The objectives were to (a) document behavioral and hormonal changes in 2 female sable antelope during the introduction, (b) compare fecal glucocorticoid metabolites (FGM) in each individual during the introduction stages, (c) measure fecal androgen metabolites (FAM) during introduction and compare with dominance rank and observed aggression, and (d) monitor estrous cycle synchronization. Results demonstrate that FGM were higher before than during and after the introduction. Behavioral observations indicated limited aggression between females, although the keeper survey results revealed that the new female was more dominant and had higher mean FGM and FAM than the resident. Both sable antelope were reproductively active throughout the year. Results indicate that fecal hormone analysis can provide zoo management with valuable information to minimize the risk of aggression, injury, and stress during introductions of nonhuman animals.     

Using Fecal Hormonal and Behavioral Analyses to Evaluate the Introduction of Two Sable Antelope at Lincoln Park Zoo

Introductions of sable antelope (Hippotragus niger) can be difficult due to the potential ensuing aggression compounded by their large horns. The goal was to use hormonal assays and behavioral analyses to evaluate the success of an introduction of 2 adult females at Lincoln Park Zoo. The objectives were to (a) document behavioral and hormonal changes in 2 female sable antelope during the introduction, (b) compare fecal glucocorticoid metabolites (FGM) in each individual during the introduction stages, (c) measure fecal androgen metabolites (FAM) during introduction and compare with dominance rank and observed aggression, and (d) monitor estrous cycle synchronization. Results demonstrate that FGM were higher before than during and after the introduction. Behavioral observations indicated limited aggression between females, although the keeper survey results revealed that the new female was more dominant and had higher mean FGM and FAM than the resident. Both sable antelope were reproductively active throughout the year. Results indicate that fecal hormone analysis can provide zoo management with valuable information to minimize the risk of aggression, injury, and stress during introductions of nonhuman animals.     

Influence of the estrous cycle on heterosexual aggression in two strains of rats (S3 and WEzob)

Two strains of rats (S₃ and WEzob), which show different levels of aggression in the laboratory, were tested in repeated heterosexual confrontations. Daily 15-min observations were made of the interactions between a female throughout a complete estrous cycle and the same male partner. In both strains the topography of aggression was similar in males and females, but the frequency of specific parameters varied. Males showed more offensive and females more defensive patterns. The overall level of aggression was very low on the day of estrous, when the female was sexually receptive. There were no differences in any elements of female or male behavior between the other 3 days of the cycle. The results support previous conclusions from single-sex encounters that in rats there is no sexual dimorphism in the ability to show aggression.     

Nonphotic phase shifting in female Syrian hamsters: interactions with the estrous cycle

Nonphotic phase shifting of circadian rhythms was examined in female Syrian hamsters. Animals were stimulated at zeitgeber time 4.5 by either placing them in a novel running wheel or by transferring them to a clean home cage. Placement in a clean home cage was more effective than novel wheel treatment in stimulating large (> 1.5 h) phase shifts. Peak phase shifts (ca. 3.5 h) and the percentage of females showing large phase shifts were comparable to those found in male hamsters stimulated with novel wheels. The amount of activity induced by nonphotic stimulation and the amount of phase shifting varied slightly with respect to the 4-day estrous cycle. Animals tended to run less and shift less on the day of estrus. Nonphotic stimulation on proestrus often resulted in a 1-day delay of the estrous cycle reflected in animals' postovulatory vaginal discharge and the expression of sexual receptivity (lordosis). This delay of the estrous cycle was associated with large phase advances and high activity. These results extend the generality of nonphotic phase shifting to females for the first time and raise the possibility that resetting of circadian rhythms can induce changes in the estrous cycle.     

Short days and exogenous melatonin increase aggression of male Syrian hamsters (Mesocricetus auratus)

Many nontropical rodent species rely on photoperiod as a primary cue to coordinate seasonally appropriate changes in physiology and behavior. Among these changes, some species of rodents demonstrate increased aggression in short, "winter-like" compared with long "summer-like" day lengths. The precise neuroendocrine mechanisms mediating changes in aggression, however, remain largely unknown. The goal of the present study was to examine the effects of photoperiod and exogenous melatonin on resident-intruder aggression in male Syrian hamsters (Mesocricetus auratus). In Experiment 1, male Syrian hamsters were housed in long (LD 14:10) or short (LD 10:14) days for 10 weeks. In Experiment 2, hamsters were housed in long days and half of the animals were given daily subcutaneous melatonin injections (15 microg/day in 0.1 ml saline) 2 h before lights out for 10 consecutive days to simulate a short-day pattern of melatonin secretion, while the remaining animals received injections of the vehicle alone. Animals in both experiments were then tested using a resident-intruder model of aggression and the number of attacks, duration of attacks, and latency to initial attack were recorded. In Experiment 1, short-day hamsters underwent gonadal regression and displayed increased aggression compared with long-day animals. In Experiment 2, melatonin treatment also increased aggression compared with control hamsters without affecting circulating testosterone. Collectively, the results of the present study demonstrate that exposure to short days or short day-like patterns of melatonin increase aggression in male Syrian hamsters. In addition, these results suggest that photoperiodic changes in aggression provide an important, ecologically relevant model with which to study the neuroendocrine mechanisms underlying aggression in rodents.