Subordinate Mice Research Articles

Effects of social housing condition and behavior on growth of the Shionogi mouse mammary carcinoma

We have demonstrated marked effects of social housing condition on the growth rate of the androgen-responsive Shionogi mouse mammary carcinoma. The present study investigated the possible role of psychosocial variables in modulating the differential tumor growth rates observed. Male DD/S mice were reared individually housed (I) or in groups (G) of three or five siblings or nonsiblings. Following tumor cell injection, mice either remained in their rearing conditions (II, GG) or were rehoused (IG, GI). Effects of group size, sibling relationship, dominance status, change vs. no change in housing condition, and direction of change (individual to group or group to individual) were examined. Home cage behaviors were monitored both prior to and following tumor cell injection and rehousing. Overall, mice in the GI conditions showed faster tumor growth rates than mice in the IG conditions. Mice in the II and GG conditions showed intermediate tumor growth rates. Differences in group size and sibling relationship prior to and following tumor cell injection and rehousing had no significant influence on tumor growth rates. However, both change in housing condition and direction of change following tumor cell injection/rehousing were significant variables in modulating differential tumor growth rates. Dominance status differentially influenced tumor growth depending on whether mice experienced a change in housing; in the IG conditions, dominant mice showed faster tumor growth whereas in the GG conditions, dominant mice showed slower tumor growth than subordinate mice. Increased fighting among mice in IG compared to mice in GG conditions may play a role in modulating differential tumor growth rates.

Effects of a short period of isolation in adulthood on the aggressive behavior of dominant and subordinate male mice

Male ddY mice were used to investigate the effect of a short period of isolation in adulthood on aggressive behavior. The relationship between the dominance status previous to isolation and the effect of isolation was investigated. The mice were kept in isolation for 3 weeks from 9 weeks of age, during which intruder tests were conducted once a week. They the went through an encounter test, in which the mice encountered dominant or subordinate mice in a neutral space. The number of the formerly-dominant isolated mice that attacked the intruder mice decreased at first and then increased. The latency to attack also lengthened at first and then shortened. Seven former-dominants continued to show aggression throughout the intruder The number of the formerly-subordinate isolated mice that attacked the intruder mice increased linearly. But 3 former-subordinates did not show aggression through the entire experiment. After 3 weeks isolation, the number of mice that showed aggression and the amount of aggression did not differ between the former-dominants and subordinatcs. Isolation housing was concluded to differentially affect the dominant and subordinate mice during the 3 weeks of isolation. It was also concluded to differentially affect the mice of absolute dominance and relative dominance differentially. The aggressive behavior of the isolated mice appears to occur independently of site.

The differential responses to the odor of unfamiliar male conspecifics in dominant, subordinate, and isolated mice

Male ddY mice were used to investigate the responses toward the odor of unfamiliar male mice. They were reared either in isolation from 3 weeks of age or in pairs. At 10 weeks of age, they went through a 4-day test period, in which the responses of the mice toward the odor of unfamiliar dominant and subordinate mice were investigated by differentiating the responses into the time to investigate the odor and the final decision of avoidance or preference. All the mice went through the encounter tests after this odor test in order to investigate the relationship between the responses toward the odor and the behavior toward the odor donor.

Differential response to the odor of familiar intruder mice in male mice (Mus musculus)

Responses to the odor of familiar intruder male mice according to their dominance were investigated. Responses were classified into 2 aspects: the investigation of the odor and the decision-making regarding avoiding it or not. The results varied according to the dominance of the respondents and the odor donor, and also according to the context of previous encounter situations. The dominants that had attacked an intruder dominant mouse responded randomly to its odor, whereas the dominants that had fought with it tended to avoid the odor. The subordinates that had observed an intruder dominant mouse being attacked by its dominant cagemate preferred the passage with the intruder's odor. The odor of a subordinate mouse was neither avoided nor preferred by either the dominants or subordinates. It was suggested that mice distinguished the dominance of the odor donor regardless of the context of the previous encounter situation, but they responded differently according to it and also according to their own dominance status.

Effects of prior agonistic experience on risk assessment and approach behavior evoked by familiar or unfamiliar conspecific odors

Risk assessment and appetitive behaviors in response to familiar and unfamiliar conspecific odors were measured in mice rendered dominant or subordinate by a series of resident-intruder encounters. Subordinate mice showed elevated levels of risk assessment in response to the odors of both familiar dominant and unfamiliar males. These behaviors were almost totally absent among dominant males exposed to familiar subordinate or unfamiliar male odors. Subordinate mice showed a marginally significant elevation in latencies to approach familiar, but not unfamiliar, dominant odors. Dominant and subordinate mice spent comparable amounts of time in the cage area containing familiar antagonist odors, however, and the durations of subordinates were mildly elevated, rather than decreased, when unfamiliar conspecific odors were present. There were no group differences in any of the appetitive behaviors. These findings suggest that apparent preferences for conspecific odors may arise from quantitatively and/or qualitatively differing emotional states. The inclusion of risk assessment measures is suggested to be a useful adjunct for studies of olfactory preference/rejection. © 1994 Wiley-Liss, Inc.

Role of anxiety in subordinate male mice sexual behavior

Dominant and subordinate male mice behave differently when exposed to a female, with subordinates showing impairment of their sexual performance in the presence of the male antagonist. In the present study, we investigate whether these rank-related behavioral differences can be modified by an anxiolytic treatment. In a first experiment, diazepam (0.25 mg/kg) improves the performance of subordinate mice toward the female, as shown by the increase of proxemic behavior, anogenital sniffing, and social grooming of the female. Social grooming of the female is the only behavior modified by a higher dose of the anxiolytic drug (0.5 mg/kg). A second experiment, in which dominant and isolated mice are subjected to the experimental procedure, demonstrates that social behavior of these two classes of males is not affected by the pharmacological treatment. The results are discussed in terms of the advantages of using subordinate males in such a sexual context as a model for the study of anxiolytic drugs.

Are there preexisting behavioral characteristics that predict the dominant status of male NIH Swiss mice (Mus musculus)?

The behavior of isolated Cr:NIH(S) mice (Mus musculus) was studied in a holeboard test of exploration, in a plus-maze test of anxiety, in the resident-intruder paradigm of aggression, and in the swim test. Thereafter, mice that were matched for body weight were housed together in groups of 4-5. Within a week, 1 mouse per cage (the alpha) had attacked all its subordinate cagemates but lacked any signs of attack itself. Subordinate mice had bite marks on their tails and backs. When mice were isolated, no differences were found between the behavior of those that later became alphas and those that became subordinates. In contrast, after the establishment of the social hierarchy, alpha mice spent less time immobile in the swim test and had higher locomotor activities than did the subordinate mice. The results suggest that the differences in behavior between the alpha and subordinate mice result from aggressive social interactions in the home cage.

Effects of the benzodiazepine receptor inverse agonist, DMCM, on the behaviour of mice: An ethopharmacological study

Ethopharmacological procedures and a two-compartment black and white test box were used to examine behavioural effects produced by the benzodiazepine receptor inverse agonist, methyl-6,7- dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), when given by intraperitoneal injection (0.4 and 1.0 mg/kg) to pair-housed adult CD1 male mice. Control mice received injections of the solvent. Behaviour in the light-dark box was examined at 30 min after the injection and behaviour during encounters with an untreated group-housed male, in a neutral cage, was then assessed by ethological procedures. In dominant mice, aggressive behaviour was significantly reduced and the ratio of flight, relative to aggression received, was significantly increased by DMCM at 0.4 mg/kg. At 1 mg/kg but not 0.4 mg/kg, DMCM decreased time spent by dominant mice in the light compartment of the test box. In both dominant and subordinate mice, flight was increased by DMCM at 1 mg/kg to a level close to statistical significance. Treatment with DMCM had no other detectable effect on the behaviour of subordinate animals. It is suggested that anxiogenic activity of this compound might induce a shift of agonistic behaviour from aggression to “fear-induced flight”.

Effects of mammalian FMRF-NH2-related peptides and IgG from antiserum against them on aggression and defeat-induced analgesia in mice

The effects of two endogenous mammalian FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides, an octapeptide F8Fa (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) and an octadecapeptide A18Fa (Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Pro-Gln-Arg-Phe-NH2 ), and IgG from serum against them on the responses to aggression and defeat-induced analgesia were examined in subordinate mice in "resident-intruder" pairings. Intracerebroventricular (ICV) administrations of F8Fa and A18Fa (0.10-10 micrograms) reduced, in a dose-dependent manner, the number of bites to obtain defeat in the subordinate mice during the agonistic encounters, as well as attenuating defeat-induced analgesia, with F8Fa having a greater inhibitory effect than A18Fa. Peripheral administration of naloxone (1.0 mg/kg) had a similar inhibitory effect on the number of bites to defeat and the level of defeat-induced analgesia. In contrast, ICV administrations of F8Fa-IgG and A18Fa-IgG antisera increased the number of bites to defeat and augmented the levels of defeat-induced analgesia, with F8Fa-IgG having a greater effect than A18Fa-IgG. These results provide further evidence that the peptides, F8Fa and A18Fa, are involved in the modulation of opioid-mediated analgesia accompanying biological stressors and suggest that these endogenous FMRF-NH2-related peptides may also be associated with the expression of opioid-sensitive components of aggressive behavior.

Effect of subordinance, lack of social hierarchy, and restricted feeding on murine survival and virus leukemia

When caged in groups of three and fed ad libitum, dominant male mice survived longer than subordinate group members which again lived longer than males caged in groups of nine, among whom no rank order was established. In groups of nine the social structure was not affected when the food supply was reduced to the lowest level not affecting survival, but in groups of three, food reduction made the survival of both dominant and subordinate animals drop to a level matching that of groups of nine. After challenge with a small dose of Moloney virus, leukemia developed among ad libitum fed subordinate mice in groups of three and members of groups of nine, but not among the dominant animals. Food restriction enhanced the leukemia incidence, but dominant animals continued to go free. We conclude that subordinace and also lack of social hierarchy result in a higher incidence of virus induced leukemia, that severe food restriction does the same, and that the effect of social order on leukemia development prevails even under feeding conditions that nearly abolish group-related differences in survival.

Male reproductive strategies in dominant and subordinate mice

Male reproductive strategies in dominant and subordinate mice

Effects of opiate agonists and antagonists on aggressive encounters and subsequent opioid-induced analgesia, activity and feeding responses in male mice

The effects of peripheral administration of the mu, kappa and sigma opiate agonists, levorphanol (1.0 mg/kg), U-50,488 (1.0 and 10.0 mg/kg), (±) SKF-10,047 (10.0 and 30.0 mg/kg), respectively, as well as the delta opiate antagonists, ICI-154,129 (10.0 mg/kg), and the prototypic antagonist, naloxone (1.0 mg/kg), on the agonistic behaviors and subsequent analgesic, locomotory and ingestive responses of subordinate mice were examined in a “resident-intruder” paradigm. The latter behaviors were examined in both defeated and nondefeated mice that had received an equivalent level of aggression. The mu and delta opiate antagonists decreased, while the mu, kappa, and sigma opiate agonists selectively increased aggressive behavior (number of bouts of aggressive interactions, number of bites to defeat, time to defeat). Both naloxone and the delta antagonist suppressed defeat- and aggression-induced activity and feeding, while only naloxone blocked the analgesic response. Levorphanol enhanced, U-50,488 had variable dose related effects, and SKF-10,047 decreased the defeat and aggressive-induced responses. These results indicate that various opioid systems and opiate receptors are differentially involved in the mediation of various components of the agonistic encounters and in the expression of the consequences of social conflict and defeat-induced opioid activation.

Inhibitory influences of the adrenal steroid, 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone [correction of tetrahydroxycorticosterone] on aggression and defeat-induced analgesia in mice.

The effects of intraperitoneal administrations of the deoxycorticosterone metabolite, 5 alpha-pregnane-, 21 diol-20-one (3 alpha, 5 alpha-tetrahydrodeoxycorticosterone; alpha-THDOC) on the responses to aggression and defeat-induced analgesia were examined in subordinate intruder male mice in "resident-intruder" pairings. alpha-THDOC reduced in a dose-dependent mannter (1-20 mg/kg) the number of bites and time to obtain defeat in subordinate mice during the agonistic encounters, as well as attenuating defeat-induced analgesia. These inhibitory effects of alpha-THDOC were separate from its sedative actions at 20-30 mg/kg. In addition, the stereo-isomer, 3 beta-pregnane-3 alpha, 21 diol-20-one (20 mg/kg) had no significant effects on the agonistic encounters and defeat, indicating that the inhibitory effects of alpha-THDOC on agonistic interactions are stereospecific. Pretreatment with the benzodiazepine antagonist Ro 15-1788 (5 and 10 mg/kg) attenuated the inhibitory effects of alpha-THDOC on defeat-induced analgesia. Ro 15-1788 (5, 10 mg/kg) by itself, however, had minimal effects on these agonistic interactions and subsequent defeat-induced analgesia. These results indicate that the naturally occurring steroid, alpha-THDOC, has significant effects on responses to aggression and defeat-induced analgesia.

Aggression, defeat and opioid activation in mice: Influences of social factors, size and territory

The aggressive components and opioid-mediated behavioral consequences of various types of intraspecific agonistic interactions between individual male mice were examined. The size of the animals, their previous social history (group or isolation housing) and territory on which the encounter took place were varied to yield 26 different ‘resident-intruder’ paradigms. In these agonistic encounters the latency to first attack, number of bites and time to defeat, as well as the number of attack bouts present varied according to the ‘resident-intruder’ paradigm employed. The behavioral consequences of aggression and defeat, including analgesia, increased activity and augmented feeding were determined from the subordinate mice in 5 representative agonistic interactions. These behavioral responses, which had been previously shown to be mediated by endogenous opioid systems also varied according to the ‘resident-intruder’ paradigm employed. When both mice were group-housed, there was no agonistic behavior, regardless of the size of the mice or the testing arena. In isolated animals the defeat posture was only observed in 1 of the 19 paradigms. It is suggested that various ‘resident-intruder’ pairings and agonistic interactions can provide a reliable and useful means of examining differential naturalistic stress-induced endogenous opioid activation.

Inhibitory influences of MIF-1 (PLG) and Tyr-MIF-1 (YPLG) on aggression and defeat-induced analgesia in mice

The effects of prolyl-leucyl-glycinamide (MIF-1, PLG), tyrosine-prolyl-leucyl-glycinamide (Tyr-MIF-1, YPLG) and the exogenous opiate antagonist, naloxone, on aggressive interactions and defeat-induced analgesia were examined in male mice. All three substances reduced the number of bites required to obtain defeat in subordinate mice during aggressive encounters, as well as blocking subsequent defeat-induced analgesia. Tyr-MIF-1 had significantly greater inhibitory effects than MIF. These results suggest that both MIF and Tyr-MIF-1 may function as endogenous opioid antagonists and have inhibitory influences on aggression, with the antagonistic effects of Tyr-MIF-1 being more potent than those of MIF-1.

An octadecaneuropeptide (ODN) derived from diazepam binding inhibitor increases aggressive interactions in mice

The effects of intracerebroventricular administrations of an octadecaneuropeptide (ODN) derived from the polypeptide, diazepam binding inhibitor (DBI), on offensive and defensive aggression were examined in male mice. During the initial period after administration (1–5 min) ODN inhibited social and agonistic behavior. At 30 min after treatment, ODN increased, in a dose-dependent manner, the incidence of and intensity of offensive aggression in dominant resident mice. ODN also increased the number of bites required to obtain defeat in subordinate mice during aggressive interactions, as well as reducing subsequent defeat-induced analgesia. These changes in offensive and defensive aggressive behavior that were induced by ODN were reduced by the benzodiazepine receptor antagonist Ro 15-1788. These results suggest that ODN has significant modulatory effects on aggression.

The Effects of Food Deprivation in Dyadic Encounters in Apodemus sylvaticus

AbstractThe nature of dominance in relationships among male Apodemus sylvaticus was investigated using multivariate analysis and by experimental manipulation of the behaviour of dominants. The behaviour of dominant mice was typified by greater frequencies and durations of exploration, approach and pursuit of subordinates in short encounters in a small arena. The direction of encounters normally remained constant over 48 h.When the dominant mouse in a dyad was deprived of food there was a change in its behaviour and an immediate change in the behaviour of the subordinate. Subordinates showed greater interest in starving, though known, dominants, explored more freely and indulged more in pursuit than control subordinate mice i. e. those matched with dominants on an adequate diet. Results suggest that in A. sylvaticus, dominance is associated with the inhibition of the activity of a subordinate and the relationship is maintained by the behaviour of the dominant rather than the deference of the subordinate.

FMRFamide, a putative endogenous opiate antagonist: Evidence from suppression of defeat-induced analgesia and feeding in mice

Social conflict and defeat in mice leads to an activation of endogenous opiate systems. The effects of intracerebroventricular administration of the peptide FMRFamide (Phe-Met-Arg-Phe-NH 2) and the opiate antagonist naloxone, on agrressive encounters, defeat-induced analgesia and defeat-induced feeding were examined in male mice. Both substances reduced the number of bites required to cause defeat in subordinate mice during aggressive encounters, as well as suppressing the subsequent defeat-induced analgesia. Administration of FMRFamide or naloxone also reduced defeat-induced feeding. These results indicate that FMRFamide (or FMRFamide-like neuropeptides) may function as endogenous opioid antagonists.

Prolyl-leucyl-glycinamide reduces aggression and blocks defeat-induced opioid analgesia in mice

The effects of Prolyl-leucyl-glycinamide (PLG, MIF-1) and the exogenous opiate antagonist naloxone, on agressive interactions and defeat-induced analgesia were examined in male mice. Both substances reduced the number of bites required to obtain defeat in subordinate mice during aggressive encounters as well as blocking the subsequent defeat-induced analgesia. These results suggest that MIF-1 may function as an endogenous opioid antagonist and have an inhibitory influence on aggression.

Splenomegaly and other hematological parameters in the socially dominant mouse

Within a social dominance hierarchy, subordinate mice show hematological changes such as increased erythropoiesis and splenomegaly. The present experiment demonstrates similar findings for the unwounded dominant mouse. In addition, total serum protein, serum albumin and plasma fibrinogen were measured. Male DBA/2j mice were placed into social triads for three 24 hr periods. The resultant dominant and subordinate mice were compared with isolated control mice. Splenomegaly, thymus involution, decreased hematocrit, and increased fibrinogen levels were found in dominant mice. Subordinate mice demonstrated the same changes to a greater extent, as well as an increased reticulocyte count. Only dominant mice showed a reduction in total serum protein. Wounding-independent processes must be involved in these cellular and non-cellular hematological effects of psychosocial stress.