Effects of neonatal treatment with cyproterone acetate on aggressive behavior induced by footshock in adult male rats

High levels of androgens are required to organize aggressive behavior in adult male rats. Footshock-induced aggression was tested in Wistar rats allocated to one of three experimental groups: control (oil-injected) males (M), males neonatally injected with the antiandrogen cyproterone acetate (CA), and males treated as in the CA group but gonadectomized just before puberty (CAG). An antiaggressive effect of CA in those adult male rats neonatally treated with this compound was found. Neonatal exposure to cyproterone acetate exerts an antiandrogenic effect over the expression of shock-induced aggressive behavior. The behavioral effects of CA were not countered by adult treatment with testosterone propionate.     

The role of endocrines in isolation-induced intermale fighting in albino laboratory mice. I: PITUITARY-ADRENOCORTICAL INFLUENCES

Recent experiments concerning the possible role of components of the pituitary–adrenocortical axis (ACTH and glucocorticoids) in isolation-induced intermale fighting behavior in laboratory strains of mice are reviewed. A series of experiments which investigate factors that may influence the successful demonstration of this relationship are described. Differences in performances in standard-opponent tests of some outbred strains of albino mice are indicated, as well as an interesting positive correlation between the aggressiveness and the relative adrenal weights of the strains employed. Long-acting preparations of both ACTH and ACTH 4–10, injected throughout a period of isolation, suppressed fighting behavior in intact TO-strain mice in subsequent standard-opponent and trained-fighter tests. After it had been confirmed that vigorous isolation-induced fighting could be obtained in bilaterally castrated mice which had been subcutaneously implanted with testosterone pellets, the effects of long-acting preparations of ACTH, ACTH 4–10, ACTH 1–10, and ACTH 4–10 D-phe on the fighting behavior of such animals were studied. A significant suppression of fighting behavior was evident only with respect to ACTH, suggesting that ACTH 4–10 may have its action on this behavior in a manner rather different from that of the parent molecule. Some evidence was also obtained indicating that the zinc used in the preparation of long-acting injections of ACTH and its analogs may also cause a decline in the level of fighting behavior, in a standard-opponent test, in TO-strain mice which had been castrated and testosterone implanted. While such a finding does not affect the validity of the recorded behavioral influences of ACTH and ACTH 4–10 described earlier, it does seem likely that the presence of this substance in placebo injections would make the demonstration of the actions of the pep tides difficult, as there would be a low level of fighting in all categories. Rather less impressive results were obtained with respect to the influences of ACTH preparations and zinc on castrated—implanted CFW mice. The studies identify a number of the factors which may influence the successful demonstration of a relationship between the functioning of the pituitary—adrenocortical axis and isolation-induced agonistic behavior in the mouse. A number of general, if tentative, conclusions may also be listed. It seems likely, in spite of the interpretational difficulties caused by what seems to be a complex and rather unstable relationship, that ACTH and glucocorticoids may have profound influences on this type of fighting behavior in this species. One may also conclude that the evidence for an extraadrenal influence of ACTH on this behavior appears stronger as a result of these and related studies and that the actions of ACTH and its analogs on murine fighting behavior may be logically related to the actions of these compounds on the acquisition and extinction of conditioned avoidance reactions in hypophysectomized rats. The possible utility of such actions to the natural territorial habit of the adult male mouse is also indicated.     

Effects of age at differential housing and the duration of individual housing/grouping on lntermale fighting behavior and adrenocortical activity in TO strain mice

A study of the effects of the duration of individual and group housing on intermale fighting and adrenocortical activity was conducted in TO strain mice. It was found that fighting and threat increased with progressive isolation up to an asymptote at 56–58 days. ‘Basal’ adrenocortical function differed little under the 2 housing conditions, but after ‘stress,’ mice isolated for short periods, which had not fought when tested for aggression, had lower titers than group-housed counterparts. However, mice that had been isolated for longer periods, and had fought in aggression tests, had higher corticosterone titers than comparable group-housed animals. The effects of a short duration (28–30 days) of differential housing, commencing at different ages, were also studied. The shorter duration adrenocortical changes were largely confirmed. In general, the earlier the age at which the differential housing was imposed, the greater the behavioral differences between animals under each housing condition. It is suggested that this is largely a consequence of a loss of behavioral plasticity in older mice. The data provides little support for the concept of the “isolation stress syndrome,” or for the view that the characteristic fighting exhibited by individually housed mice is a consequence of “social deprivation”.     

Relationship between sexual activity and intraspecific fighting in male mice

Significantly more male mice having cohabited and mated with intact females subsequently displayed intraspecific fighting behavior after castration than males having cohabited with noncycling (ovariectomized) females. Also, intact males that failed to achieve a criterion for aggression during three screening tests subsequently showed a marked increase in fighting after having had copulatory experience relative to males that lived with ovariectomized females. Lastly, spontaneously aggressive males copulated more frequently than nonfighters.     

Effects of alpha and beta adrenergic antagonists on aggressive behavior in male mice

The effects of a variety of alpha and beta adrenergic antagonists were examined on the social encounters of isolated male mice with anosmic male partners. A range of alpha antagonists, including phentolamine, prazosin, and yohimbine, all suppressed social aggression. A range of beta antagonists, including propranolol, atenolol, metaprolol, and ICI 118, 551, also reduced this type of attack. Ethological assessment of the lowest effective dose of these adrenergic antagonists revealed a marked inhibitor action on offensive, social, and nonsocial behavior, while defensive responses and immobility were enhanced. It is concluded that the noradrenergic system has a significant non-specific role in mediating intermale aggression via both alpha and beta adrenergic receptor subtypes. © 1993 Wiley-Liss, Inc.     

Female behavior in populations of mice in the presence and absence of male hierarchy

Female aggression may be the regulator of population size in small mammals. Freely growing populations of house mice showed several differences in aggressive female behavior in the presence and the absence of a male hierarchy. Territoriality in females and not in males appeared to maintain social order and regulate population density. Certain females were seen patrolling and guarding the territory and chasing and fighting with both male and female intruders. These females did not fight amongst themselves, suggesting that they were not fighting for rank (as do the males) but for territory. Although these aggressive females produced young, the pups were neglected, and few were weaned. The non-aggressive females were the successful breeders. Aggression by the females only occurred when there was reproduction and increased densities. Assembled females with no males present never show this aggression. The occurrence of “male-type” behavior became most apparent when the males were removed at peak population densities. The removed males were then castrated and injected with testosterone cyprionate. Doses were increased by population cage, and therefore all males returned to each freely growing population were given the same dose. The males given oil placebo injections showed no return of a male hierarchy and the females showed high levels of aggression toward them. Males injected with testosterone cyprionate showed return of male aggression and fighting and mounting of females. But the new “dominant” females continued their patrols and chased males away from their territories and did not permit these males to mount. Male-male fighting consisted primarily of frontal attacks to the face and roll and tumble fights. Female-male aggression consisted primarily of attacks to the posterior region targeted at the base of the tail and the genitals of the male. The males were rarely seen attacking females and then only during mating. Females only attacked each other in defense of their territories.     

The role of endocrines in isolation-induced lntermale fighting in albino laboratory mice. II. Sex steroid influences in aggressive mice

Isolation-induced intermale fighting in laboratory mice can be dramatically reduced under most circumstances by castration. This behavior in castrates may, however, be restored, or even accentuated, by androgen replacement. Experiments on the effects of sex steroids on such fighting in castrated mice, which, for want of a better term, are designated as “aggressive,” have been recently described. These mice are housed with a female until 10 days after siring a litter and are, thereafter, housed individually for a further 14 days before castration and subsequent hormone treatment. Such mice show substantial levels of fighting in “standard-opponent” tests even before isolation. Although castration results in reduced fighting in these mice, this behavior is rarely completely abolished in all individuals. It seems likely that steroid treatment of aggressive mice maintains or intensifies an already present motivation. Treatments in these studies consisted of daily oil-based intramuscular injections for 14 days preceding and throughout behavioral testing. The standard-opponent tests were 7 min encounters with adult, subordinate, grouped males in the cleaned home cages of experimental mice. The steroids investigated included estradiol benzoate (EB), 19-hydroxytestosterone (19-OHT), androstenedione (A), testosterone (T), and Sα-dihydrotestosterone (DHT), either singly or in combination. The results suggest that (a) on a dosage basis, estrogens were at least as effective as androgens in maintaining fighting in castrated aggressive mice; (b) 19-OHT (one of the metabolic intermediates between testosterone and 17 β-estradiol) was also effective but somewhat less so than the same dose of EB; (c) the three naturally occurring androgens investigated all effectively maintained fighting at comparatively low doses (50 μg/day) which compares with a replacement dose of 500 μg/day of T in some studies in traditional castrated mice (e.g., Luttge and Hall, 1973); (d) aromatization is not essential for a behavioral action of androgens as DHT, a nonaromatizable androgen, maintained fighting in these mice; (e) whereas a two-site (central motivational and peripheral penile) action seems probable in the influence of androgens on sexual behavior in castrated rats (e.g., Parrott, 1975), DHT did not augment the action of EB on fighting in castrated aggressive mice, indicating that only a central action of steroids was required in the aggressor.     

Intermale fighting and predatory behavior in house mice: An analysis of behavioral content

Two forms of aggression, intermale and predatory, wwere compared on the basis of behavioral content. Male wild mice were presented with opponents of two types, nonaggressive male mice and crickets, and the amounts of time spent in each of 18 behaviors were recorded. Results from analyses of variance and principal components analyses indicated that the structure of behavioral content differs greatly for intermale fighting and predatory behavior. It was, therefore, concluded that the integrated patterns of beahvior were controlled by separate mechanisms for predatory versus intermale aggression.     

The development of territorial-induced intermale agonistic behavior in albino laboratory mice

Male mice of the CF-1 strain (Mus musculus) were allowed to take up lone residence in a small territory consisting of a 60-cm enclosure attached by a tubular runway to a standard mouse cage with food, water, and bedding. A group of ten mice, each of which resided in its own separate enclosure for 24 hours, were more aggressive toward intruders than other groups of ten mice following six-hour residence periods, or no such residence. Aggression toward intruders increased in repeated weekly tests of the six-hour residents, but after four weeks of testing did not reach the maximum stable level displayed by the 24-hour residents over four weeks of testing. In another experiment, the 24-hour residence period of groups of 20 CF-1 male mice was disturbed by briefly removing the mouse from the enclosure, before introducing the intruder, at various intervals prior to testing. Removal of the resident five minutes before testing resulted in a marked decrease in aggression toward intruders. Although lesser decreases in aggression followed intervals of 30, 45, and 60 minutes, a 180 minute interval resulted in no appreciable effects compared to undisturbed controls. It is concluded that exposure to the stimuli provided by the enclosure results in an aggressive readiness in the resident mouse which reaches a high level within a 24-hour period.     

Effects of early exposure to mating on adult sexual behavior in male mice varying in their genetic disposition for aggressive behavior

This study examined whether the sexual behavior of adult male mice is influenced by exposure in early postnatal life to brief episodes of mating. Another focus of interest was the interplay between a genetic disposition for aggressive behavior and the early exposure experiences. The subjects used in the study were male mice of the fiftysixth generation of selection for high (Turku aggressive, TA) and low (Turku non-aggressive, TNA) levels of aggressiveness. Moderately aggressive males of the parental strain (normal, N) were also used. Subjects of each strain were exposed from 21 to 32 days of age to mating mice behind a wire mesh screen. Control subjects were placed in a comparable enclosure, but were exposed to nothing. The results showed that male mice exposed to mating early in life showed a higher rate of activities in the sexuality tests, including aggressive responses. A genetic potential for aggressive behavior was related to a higher degree of sexual activity, and the early exposures optimized the hereditary attributes. The relation between sexual and aggressive behavior is discussed. © 1994 Wiley-Liss, Inc.     

Selective approach to a male and subsequent receptivity to mounting comprise mate‐choice behavior of female mice1

Abstract: To ensure the effectiveness of the mate‐choice behavior of female house mice (Mus domesticus), we observed them in two different situations that involved restriction of the area of movement of the male mice. In Experiment 1, we observed 12 trios consisting of two male mice and an estrous female placed in a chamber in which none of the animals was restricted during the 6‐h test. It was found that the female was more receptive to the male that had ejaculated with it first. Additionally, when the female initiated the mating event by approaching the male, the lordosis quotient was higher than that when the male initiated the mating event. In Experiment 2, a female was able to visit two males that were prevented from getting out of small boxes. As a result of the 3‐h observation of 10 cases, it was found that the females were more receptive to the dominant male. The intromission ratio of the dominant male was also higher than that of the subordinate male. The behavioral roles of female mice in mating interactions and their adaptive validity are discussed.     

Gender-specific social experiences and the development of aggressive and sexual behavior in male mice

This study examined influences of gender-specific social experiences on the development of aggressive and sexual behavior in male mice. To determine the effects of gender-specific social experience three different types of groups were constituted after the animals had been weaned. The subjects were randomly assigned to different treatments. Female groups were composed of one experimental male and three female cohabitants. Male groups were composed of five experimental males each, and the mixed-sex groups were composed of two experimental males and of two females. The experimental subjects stayed in these groups until the age of approximately three months, when the testing for sexual and aggressive behavior commenced. For the sexuality tests, a receptive female was placed in the home cage of the experimental male for ten minutes. A nonaggressive male was placed in the home cage of the experimental male for seven minutes for the aggression tests. The experimental males were administered both sexuality and aggression tests, the sequence of testing sexual and aggressive behavior was systematically varied in order to control the influence of the two different types of behavioral tests. The results showed that males with only male social experiences showed fewer responses and were less active in both the aggression and sexuality tests than the males from the two other types of groups. Significant positive correlations between activity during aggression and sexual tests were obtained for all three groups. © 1994 Wiley-Liss, Inc.     

Infanticide and maternal aggression: Synchrony of male and female reproductive strategies in mice

Thirty-six percent of male mice from three strains attacked newborn pups sired by another male. No male attacked its own offspring. Females did not show differential aggression toward males likely (strangers) or unlikely (sires) to attack their pups. Both forms of aggression were unaffected by housing in rooms which did or did not contain the aggression targets. The three strains differed in strength of maternal aggression but not in the incidence of infanticide. Females showed more aggression when mated with males of the same, rather than a different, strain but no differences with intruders of the same or a different strain. Infanticide by males is best viewed as a postcopulatory, intermale-competition strategy, and maternal aggression as a counter strategy.     

Effects of early exposure to intermale aggression on the aggressiveness of adult male mice varying in their genetic disposition for aggressive behavior

This study examined whether adult male aggression is influenced by either visual or olfactory exposure in early postnatal life to brief episodes of aggression. Another focus of interest was the interplay between a genetic disposition for aggressive behavior and early exposure experiences. The subjects used in the study were male mice of the 49th generation of selection for high (Turku Aggressive, TA) and low (Turku Non-Aggressive, TNA) levels of aggressiveness. Moderately aggressive males of the parental strain (Normal, N) were also used. Subjects of each strain were exposed from 21 to 32 days of age to fighting males either behind a wire mesh or glass screen. Control subjects were isolated during the entire experimental period. At 90–100 days of age, each subjects was tested three times for its aggressiveness. Exposure to fighting males behind a wire mesh screen enhanced later aggressiveness of juvenile male mice. Juveniles exposed solely to visual cues were comparable to isolates, both groups showing less adult aggression. Early experience and the genetic disposition for aggression were correlated; TA males showing the greatest increase in aggressive behavior. The role of early olfactory learning is discussed. © 1993 Wiley-Liss, Inc.     

Comparison of agonistic behavior in individually-housed male mice with those cohabiting with females

Videotape recordings of male mice group-housed, individually-housed and cohabiting with females, were rated for their agonistic behavior in a “standard opponent” test. Previously mated male mice showed more fighting than isolated or grouped males. Marked differences in other social and non-social behaviors, which could not be accounted for in terms of increased fighting, were not evident. These results suggest that agonistic behavior may be usefully studied by examining male mice that have cohabited with females. One obvious advantage is that such mice cannot be dismissed as being “socially deprived,” as is sometimes claimed for individually-housed mice. Other advantages are that aggressiveness is induced quickly, at high levels, and the mice appear very sensitive to hormone manipulation following castration.     

Effects of acute administration of nicotine and lobeline on agonistic encounters in male mice

The effects of acute administration of two nicotinic ligands, (‐)‐nicotine and (‐)‐lobeline were examined on isolation‐induced aggression in mice. Individually housed male mice confronted anosmic “standard opponents” in a neutral arena 10 min after drug administration. Encounters were videotaped and evaluated using an ethologically based analysis facilitating estimation of time allocated to 11 broad behavioral categories. Nicotine did not have significant effects on threat or attack but significantly diminished time allocated to digging. The lowest dose of lobeline significantly diminished attack and induced a slight increase of immobility without significantly diminishing other behaviors with motor components. The intermediate and highest dose of lobeline reduced time allocated to all behaviors with motor components. It is concluded that these two nicotinic agonists produce different behavioral profiles during agonistic encounters in mice but that this test may not facilitate assessing the impact of such drugs on irritability. Aggr. Behav. 26:376–385, 2000. © 2000 Wiley‐Liss, Inc.     

Some adrenal correlates of aggression in isolated female mice

Forty-six female mice (CFW) were isolated for a period of 23 weeks. The effect of isolation on fighting behavior was tested weekly by introducing a naive brown female mouse into the subject's home cage. Total leucocyte counts were obtained at 8 and 14 weeks of isolation. The appearance of leucopenia was used as an index of elevated adrenocortical activity. After 23 weeks of isolation all animals were sacrificed by decapitation. Plasma was collected for corticosterone assay, and paired adrenals were used to assay catecholamine levels. On the basis of the frequency and/or the absence of fighting, the mice were segregated into fighters (n = 22) and non-fighters (n = 17). Analysis of the data by Pearson's product moment correlation and Student's t-test showed that elevated sympathetic-adrenal activity was positively correlated with aggression and that elevated adrenocortical activity was negatively correlated with aggression.     

Differences between two strains of mice,selectively bred for high and low aggressiveness,in the capacity of male odors to affect aggressive behavior

The connection between a genetic disposition for aggressive behavior and the odor signal system in male mice was studied. The males belonged to two strains of mice which have been developed by selective breeding for high- (TA) and low aggressiveness (TNA). Urine from the high aggressive strain (TA), when applied to castrates, stimulated the aggressiveness of NMRI males while TA-soiled bedding suppressed their aggressiveness. In response to male odors from the low aggressive strain (TNA), the NMRI males showed quite contrasting reactions. The results provide evidences of a correlation between the hereditarily determined disposition for aggressive behavior and the odor signal system in TA- and TNA males.     

Play fighting and the development of agonistic behavior in male and female rats

Two longitudinal studies were conducted to quantify the social behaviors exhibited by both male and female Long-Evans rats from the immediate postweaning period until young adulthood. In Experiment 1, male sibling pairs engaged in a high level of play fighting during the early juvenile period but such activity declined to a level significantly lower than that of female and mixed-sex pairs after 54 days of age. In Experiment 2, social exchanges during maturation were examined during the presence and absence of the piloerection response in an effort to distinguish play fighting from agonistic interactions. In male pairs, piloerection was rarely seen before 55–75 days of age but thereafter occurred with increasing frequency especially among dominant males. Furthermore, subordinate males retreated from their dominant partners and remained in an escape chamber for a significant amount of time only during encounters involving the exhibition of piloerection. This finding suggests that piloerection can be useful in identifying play and aggressive interactions. In female and heterosexual pairs, piloerection was observed infrequently during social encounters occurring throughout maturation. In addition, when given the opportunity to escape, females were less likely to retreat from play activity if their partner was another female than a male.