The inhibitory effects of fluprazine on parental aggression in female mice are dependent upon intruder sex

Lactating resident mice respond differently to male and female intruder conspecifics, showing defensive attack towards the former and offensive attack towards the latter. The effects of fluprazine (1-5 mg/kg) on this differential response pattern have been assessed. Although fluprazine increased the latencies of attack on male intruders, a very much more potent inhibitory effect was observed on attacks directed towards female intruders. Fluprazine also modestly reduced social investigation of female intruders and increased nest-oriented behaviour irrespective of the intruder's sex. As the pattern of attack on intruders, exploration, fear responses and maintenance behaviour all remained largely intact under drug treatment, it seems unlikely that the drug's inhibitory action on attack involves fear potentiation and/or olfactory impairment. It is suggested that the greater sensitivity of offensive attack to the inhibitory actions of fluprazine may reflect the relative degree of threat to resident parental investment posed by male and female conspecific intruders.     

Melatonin and the adrenal cortex: relationship to territorial aggression in mice

The behaviour of male TO mice on confrontation after a period of group housing (3 mice/group) was recorded, both in terms of group and individual aggression measures. A series of treatments was carried out aimed at identifying the relative contributions of corticosteroids (CS) and melatonin (MEL) to control of fighting. Adrenalectomy (ADX) and aminoglutethimide injections (AMG) were used to reduce CS both chronically and acutely, and repeated restraint stress (RES) to increase CS levels chronically. MEL was administered daily (5 days), alone or in combination with other treatments. Control group treatments included sham operation for ADX (SO), and the appropriate saline injections. Untreated groups were also tested. AMG and ADX reduced aggression to a similar extent on all measures. MEL potentiated fighting, but this effect was reversed when given in combination with ADX or AMG. RES was associated with a significant shift towards submission on individual measures, but no significant change in group measures. RES+MEL treatment did not cause any significant changes. SO animals behaved normally, but again, the aggressogenic MEL effect was not seen after SO + MEL. The results are interpreted in terms of partial inhibition of CS output by MEL.     

Fluoxetine treatment decreases territorial aggression in a coral reef fish

Serotonin is an important neurotransmitter in the regulation of social interactions in many animals. Correlative studies in numerous vertebrate species, including fishes, indicate that aggressive males have lower relative serotonergic activity than less aggressive males. We used fluoxetine, a selective serotonin reuptake inhibitor, to experimentally enhance serotonergic neurotransmission in a territorial coral reef fish and test the role of this neurotransmitter in mediating aggressive behavior and dominance interactions. The bluehead wrasse, Thalassoma bifasciatum, has a complex social system in which large males aggressively defend spawning territories from intruders. In separate experiments, we tested the effects of chronic and acute fluoxetine treatments on aggressive behavior using a resident-intruder design. In a laboratory experiment, males treated daily with intraperitoneal fluoxetine injections for 2 weeks (6 microg/g bw) displayed fewer intruder chases than saline-treated controls. Chronically fluoxetine-treated males also showed lower levels of activity than saline controls prior to intruder trials. However, activity was not correlated with chases on an individual level, indicating the lower aggression displayed by fluoxetine-treated males was not due solely to general reductions in behavioral display. A field study exposed males to a confined territorial intruder following single intraperitoneal injections of fluoxetine (10 microg/g bw) or saline given to the same individual on different days. The frequency of aggressive chases following acute fluoxetine treatment was significantly lower than that following saline injections. This study experimentally supports the link between serotonin and aggressive behavior in fishes in both a controlled laboratory testing environment and the animal's natural habitat.     

The role of androgens in the mediation of seasonal territorial aggression in male Siberian hamsters (Phodopus sungorus)

Testosterone (T) mediates aggression in a wide range of species. In some species, however, aggressive behavior persists or increases during the non-breeding season when T levels are relatively low. Animals that do not display a positive correlation between aggression and gonadal steroids suggest the need for further investigation of alternative neuroendocrine mechanisms mediating seasonal aggression. Siberian hamsters (Phodopus sungorus) are an ideal study system because they display increased territorial aggression during the non-breeding season which may be independent of circulating T levels. The goals of the present study were to: 1) explore the role of T in the aggression of reproductive males, and 2) test the hypothesis that the adrenal steroid dehydroepiandrosterone (DHEA) acts as an endocrine regulator of seasonal aggression. In Experiment 1, individuals were housed in long day (breeding) photoperiod and received castrations, exogenous T capsules or both manipulations. In Experiment 2, animals were housed in either long or short days (non-breeding) photoperiod and received DHEA or empty capsules. In both experiments, serum hormone levels and aggressive behavior were assessed. In Experiment 1, castration did not reduce aggression whereas exogenous T actually inhibited aggressive behavior. In Experiment 2, short-day individuals were more aggressive than long-day animals but DHEA treatment did not affect aggressive behavior, regardless of photoperiod. The present study supports the hypothesis that circulating gonadal steroids are not necessary to activate aggressive behavior in adult male hamsters. Further, seasonal changes in territorial aggression appear independent of circulating levels of DHEA in Siberian hamsters.     

Effect of reciprocal cross-fostering on aggression of female mice toward lactating strangers

Reciprocal cross-fostering of mice was carried out between an inbred strain (C57 BL/6) in which the female showed a particular form of aggression toward lactating female intruders, and a strain (C3H/He) which proved to lack totally this type of attack. In adulthood, cross-fostered females of the 2 strains and their controls were submitted to a series of aggression tests. They encountered in the test situation either a strange lactating female of their own strain or one of the foster strain. No differences in aggression measures were found between cross-fostered animals and controls, indicating that experiential factors (viz., cross-fostering) were without effect.     

Possible interaction of melanocyte-stimulating hormone (MSH) and the pineal in the control of territorial aggression in mice

The fighting of male mice (TO), housed in groups (3 + 3), was observed and a group aggression score (attacks/latency) recorded. There was no significant difference between the scores of untreated and saline injected groups. Pinealectomy (PX) and MSH injections (100 μg/kg IP) potentiated fighting, and raised the aggressiveness of PX groups to control level. Combined injections of MSH + MT increased aggressive behaviour to the same extent as did MT alone. MSH + PX treatment did not suggest that the two anti-aggressive treatments were additive: these groups fought less than controls, but not less than after either treatment alone. Sham operated (SO) groups fought as much as the MT injected ones, and MSH reduced this response to control levels. No consistent pattern was found in the effects of the treatments on open field activity, tail-pinch responding, or body, adrenal and testicular weights. The results support the hypothesis that the anti-aggressive effect of MSH is due to inhibition of pineal MT secretion. The increased aggressiveness shown by SO groups is assumed to be caused by leakage of MT from a partially damaged pineal.     

Ovarian hormones and their role in aggression inhibition among male mice

The role of ovarian steroids in the inhibition of isolation-induced aggression (defined here as fighting or threatening behavior) in male mice was studied, as well as the possibility of interspecies action of mammalian pheromones. Male mice were paired and tested for aggressiveness after being smeared with urine from female mice, rats, rabbits, and humans. Urine from intact and sexually mature animals caused a decrement in aggression, while ovariectomized or sexually immature animals did not produce an aggression inhibiting urine. Urine from ovariectomized animals given injections of estradiol (0.1 mg/day) for 5 days, and other estrogens caused non-aggression. Heavy perfume did not stop aggression, supporting the theory that non-aggression is not the result of simple masking of male odors. Progesterone (1 mg/day for 5 days) was ineffective in inhibiting aggression. An interspecies action of this aggression inhibiting pheromone appears to exist among mice, rats, rabbits, and to some degree, humans.     

Intruder gonadectomy and elicitation of territorial aggression in the rat.

Long-Evans rats (male castrates, female castrates, and intact males) were compared for aggression eliciting qualities in a test of conspecific territorial aggression. Mature resident males, known to reliably attack male intruders, were presented with each type of intruder in a latin-square design with replications. Intact and castrate males were both attacked and sustained numerous wounds, whereas castrate females were subject to intensive social-investigatory behaviors but were not attacked. Intact males were severely attacked, with one-third killed by bite wounds. Castrate males were also attacked but sustained fewer wounds and no deaths. Apparently, castration decreases intensity of resident aggression but fails to block the discrimination of male characteristics eliciting attack.     

The role of asymmetrical frontal cortical activity in aggression

Aggression correlates with relatively greater left than right frontal electroencephalographic activity (inverse of EEG alpha power). The present experiment extends this research by manipulating frontal asymmetry and examining its effect on aggression. Participants were assigned to increase left frontal activation or increase right frontal activation by contracting their contralateral hand. They then received insulting feedback and played a game in which they could aggress toward the person who insulted them. Right-hand contractions caused greater left than right central and frontal activation and aggression as compared to left-hand contractions. Within the right-hand contraction condition, greater relative left frontal activity was associated with greater aggression.     

Social interactions tune aggression and stress responsiveness in a territorial cichlid fish (Archocentrus nigrofasciatus)

We examined the relative influences of pre-fight housing condition, contest intensity, and contest outcome in modulating post-fight stress hormone concentrations in territorial male convict cichlids (Archocentrus nigrofasciatus). Individuals were housed either in isolation or in semi-natural communal tanks. Pairs of male cichlids that differed considerably in body mass were selected from the same housing regime. Pre-fight water-borne cortisol levels were obtained before allowing the dyad to interact until contest resolution, after which time post-fight cortisol levels were obtained from the winner and loser. There were no outcome-related differences in post-fight cortisol concentrations following escalated or non-escalated contests, a result that held true for both housing regimes. Pre-fight cortisol levels were significantly higher than post-fight cortisol levels, suggesting that initial confinement in a beaker for the water-borne hormone samples was a stressor, but that the animals acclimated quickly to confinement. Fights involving previously isolated participants were significantly more intense than those involving group-housed animals, which we explain as being a function of established relationships between social isolation, heightened acute cortisol responsiveness, and the expression of excessive aggressive behavior. Only group-housed losers demonstrated the ability to modulate aggression or hypothalamic-pituitary-interrenal (HPI) activity in a graded fashion to acute increases in cortisol or changes in contest intensity, respectively. We discuss a variety of factors that could disrupt the ability of isolates to appropriately modulate interactions between social behavior and the HPI axis, and we examine a number of functional hypotheses underlying the sensitivity of group-housed losers to changes in contest dynamics.     

Female discrimination of male dominance by urine odor cues in hamsters

Female hamsters have been found to differentially respond to the odors of dominant as opposed to subordinate males. This study reexamined these responses in an olfactometer allowing the females to choose between urinary odors obtained from males differing in dominance status and clean air source. The behavior of the estrous females was consistent with previous research which indicated that such females exhibit a preference for stimuli obtained from dominant males. Contrary to previous findings in a two-choice apparatus, diestrous females failed to prefer the odors of subordinates. These females spent significantly more time in the area infused with unscented air. These data emphasize the importance of odor cues as they relate to male attractivity and possibly mate choice. They also underscore the need to allow animals to avoid conspecific odors in order to reduce the possibility of forcing animals into an unrealistic choice situation.     

The relationship between blood alcohol levels and aggression in mice

Previous reports of the impact of ethanol on murine aggression have produced inconsistent findings; some workers have found that low doses of ethanol increase aggression whereas others have reported either no effect or a suppression. The present study examined one variable that may help to account for these inconsistencies, namely the level of blood alcohol at various times after administration. Acute doses of 0.5, 1, 2 g/kg ethanol all potently suppressed fighting in mice. However, there was no simple relationship between blood alcohol levels and fighting. It appeared that the level of blood alcohol, whether these levels were falling and the time since alcohol was cleared from the blood were all factors that influenced the drugs anti-aggressive influence.     

Ultrastructure and morphometry of the urethral glands in normal,castrated, and testosterone-treated castrated male mice

Recent studies of the urethral glands in the male mouse and rat have suggested that they are testosterone-dependent glands that may be potential sites for secretory immunity in the male genital tract. In the present study we describe the ultrastructural features of these glands in normal mice and provide quantitative data on the sizes of the acinar cells and their organelles in sham-, oil-, and testosterone-treated castrated mice. Acinar cells in urethral glands from normal mice contain numerous secretory granules, prominent Golgi complexes, elongated mitochondria, and an abundance of rough endoplasmic reticulum (RER) with large and dilated cisternae, all of which are features characteristic of secretory cells. In some acinar cells the cisternae of the RER were filled with closely packed, unbranched, straight, tubular structures that were oriented parallel to one another, that radiated from aggregates of dense material, or that were randomly attanged. In other acinar cells the cisternae of the RER showed a network of branching and anastomosing vesicular-like structures whose limiting membranes were occasionally seen in continuity with the membranes of the RER. Secretory acini showed large, unbranched tubules in the acinar lumen. When cut at right angles the large tubules exhibited a distinct fuzzy outer coat with fine projections radiating outwards. The ultrastructure of the acinar cells and the presence of tubules in the lumen suggests that they are engaged in secretion of a tubular protein. Morphometric analysis of acinar cells in the urethral glands showed that the mean volumes of nuclei, cytoplasm, secretory granules, vacuoles, and mitochondria were significantly reduced in castrated mice in comparison to either normal or testosterone-treated castrated mice. This confirms earlier observations that the urethral glands are targets of testosterone. © 1993 Wiley-Liss, Inc.     

A critical role for phagocytosis in resistance to malaria in iron-deficient mice

Both iron-deficient anemia (IDA) and malaria remain a threat to children in developing countries. Children with IDA are resistant to malaria, but the reasons for this are unknown. In this study, we addressed the mechanisms underlying the protection against malaria observed in IDA individuals using a rodent malaria parasite, Plasmodium yoelii (Py). We showed that the intra-erythrocytic proliferation and amplification of Py parasites were not suppressed in IDA erythrocytes and immune responses specific for Py parasites were not enhanced in IDA mice. We also found that parasitized IDA cells were more susceptible to engulfment by phagocytes in vitro than control cells, resulting in rapid clearance of parasitized cells and that protection of IDA mice from malaria was abrogated by inhibiting phagocytosis. One possible reason for this rapid clearance might be increased exposure of phosphatidylserine at the outer leaflet of parasitized IDA erythrocytes. The results of this study suggest that parasitized IDA erythrocytes are eliminated by phagocytic cells, which sense alterations in the membrane structure of parasitized IDA erythrocytes.     

Superantigenic characteristics of mouse mammary tumor viruses play a critical role in susceptibility to infection in mice

Mouse mammary tumor viruses (MMTV) are retroviruses that induce mammary carcinomas. An interesting feature of these viruses is the superantigen (SAg) encoded in an open reading frame within the 3′ long terminal repeat. The mechanism by which ingestion of milk-borne virus results in infection of the host mammary tissue remains incompletely understood. However, a working model has been proposed in which the interaction between viral SAg, T-cell receptor and MHC class II I-E facilitates viral replication and hence infectivity. In this review we summarize current studies demonstrating the role of SAg stimulation in susceptibility to MMTV infection.     

Activation of aggression in female rats by normal males and by castrated males with testosterone implants

Female hooded rats were continuously housed with an intact male, a castrated male with subcutaneous testosterone implants, or two other females. At weekly intervals over a 10-week period, the cagemate(s) and pups were removed and aggression by the female toward an unfamiliar female intruder was observed over a 15-min period. On the 11th week each female was subjected to this intruder test in an unfamiliar cage. On the 12th week, a final test was conducted in each female's living cage with a male rather than a female as the intruder. The aggressive behaviors recorded were attacks, bites, on-top, and piloerection. Females housed with normal males displayed a significant increase in aggression prior to parturition. Their aggressiveness persisted through the 10th test with peaks at parturition and the start of lactation. Females housed with castrated males also displayed significant increases in aggression but without the peaks associated with parturition and lactation. Their aggressiveness also persisted throughout the test period. Females housed with other females showed a small increase in aggression over weeks. All groups showed virtually no aggression in the unfamiliar cage. All females displayed some aggression toward a male intruder but the level of aggression was highest in maternal females. The results demonstrate that aggression qualitatively similar to that displayed following parturition and during lactation can be elicited in nulliparous females.     

The inhibitory effect of preexposed olfactory cues on intermale aggression in mice

To explore the effect of preexposure of olfactory cues on aggressive behavior, adult male mice, isolated for 14 days prior to the experiment, were preexposed for 10 days to one of 3 odors: (1) that of the opponent encountered in the test trial; (2) that of a strange mouse not subsequently encountered; and, (3) that of a neutral substance. The results show the greatest amount of aggression, as measured by latency to attack, accumulated attacking time, number of attacks and intensity of fighting, in the neutral preexposure group; an intermediate amount of aggression in the group preexposed to the irrelevant mouse odor; and the least amount of aggression in the group preexposed to the odor of the future-opponent mouse. Furthermore, preexposed animals in the third condition did not respond to attack by assuming the characteristic submissive posture. Results are discussed in terms of learned habituation to the pheromone which purportedly elicits aggression in the mouse.