Behavioral profile of L–741,741, a selective D4 dopamine receptor antagonist,in social encounters between male mice

Although the role of dopamine D1–D2–D3 receptors in the modulation of aggression has been extensively documented, there is not information with respect to the implication of D4 receptor. The aim of this study was to examine the acute effects of L–741,741 (0.75, 1.5 and 3 mg/kg, i.p), a selective D4 receptor antagonist, on social encounters between male mice using an ethopharmacological approach. Ten min of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. These encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioral categories was estimated. Besides other behaviors, the aggressive and motor behaviors were evaluated 30 min after injection using an ethologically based analysis. L–741,741 did not affect significantly offensive behaviors (threat and attack), as compared with the control group. Likewise, motor and anxiety‐related behaviors (such as social investigation, avoidance/flee or defense submission) were not altered after drug administration. These results suggest that dopamine D4 receptor is not involved in the modulation of aggressive behavior. Aggr. Behav. 29:552–557, 2003. © 2003 Wiley‐Liss, Inc.     

Effects of acute,subchronic and intermittent MDMA (‘ECSTASY’) administration on agonistic interactions between male mice

Recent studies suggest that acute administration of 3,4‐methylenedioxymethamphetamine (MDMA), an amphetamine derivative popularly known as “ecstasy,” produces an antiaggressive effect in male mice. However, there is no evidence with respect to the development of tolerance or sensitization after its subchronic or intermittent administration. In this study, we examined the action of low to moderate doses of MDMA (1.25, 2.5 and 5 mg/kg, i.p), administered acutely, subchronically (for 7 days) or intermittently, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic “standard opponents” 30 minutes after the drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Acute treatment with MDMA provoked a significant reduction of aggressive behaviors, without altering immobility. However, this action was only selective at 1.25 mg/kg. With the intermediate (2.5 mg/kg) and the highest doses (5 mg/kg) of the drug, it was observed a significant decrease of offensive behaviors, accompanied by an increase of exploration from a distance, avoidance/flee and defense/submission behaviors. This ethopharmacological profile could indicate the existence of an anxiogenic‐like effect of MDMA. The overall picture of the effects of MDMA was very similar in the acutely, intermittently and daily treated animals. No tolerance or sensitization to the actions of the drug was developed after its repeated or intermittent administration.     

Effects of prenatal cocaine and genotype on intermale agonistic behavior in Mus musculus

We exposed the pups of three F₁ genotypes of mice to a daily regime of cocaine by injecting their mothers (all C57BL/10J strain) on days 7–18 of gestation with 20 mg/kg subcutaneously. Pups of the cocaine and control groups did not differ on measures of maternal and pup health or size. Male pups were weaned and isolated at 21 days of age and their behaviors measured in an intermale aggression situation at about 80 days of age. Treated and untreated males of each F₁ genotype were paired in dyads with either a C3H/HeJ (hawk-like) or AKR/J (retaliator-like) standard tester male. Standard tester males were not exposed to cocaine. Cocaine treatment alone reduced the overall level of aggression in dyads, and in interaction with genotype or the standard tester it altered the behavior of dyads in all phases of social interaction: the initiation, content, and outcome. Standard testers used as behavioral probes, differentiated cocaine and control males with respect to their stimulus and behavioral qualities. Aggr. Behav. 23:183–196, 1997.© 1997 Wiley-Liss, Inc.     

Association between intermale aggression and genetically-defined tryptophan hydroxylase activity in the mouse brain

The relationship between the genetically defined intensity of intermale aggression and the activity of brain tryptophan hydroxylase (TPH) has been studied in inbred mice. No association between the enzyme activity and the percentage of aggressive mice (reflecting the predisposition to aggressive reaction) was revealed. However, a significant positive interstrain correlation between brain TPH activity and accumulated attacking time (reflecting fight intensity) was identified. No correlation was found between TPH activity and the accumulated attacking time in segregating F2 (BALB × C57BL) mice. In conclusion, TPH is an important, but not the only factor controlling the intensity of intermale aggression in mice. © 1996 Wiley-Liss, Inc.     

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.     

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.     

Effect of MAO A deficiency on different kinds of aggression and social investigation in mice

Monoamine oxidase A (MAO A) degrades serotonin, dopamine and noradrenaline, factors critically involved in the regulation of aggression. Different kinds of aggression were investigated in Tg8, a transgenic mouse strain lacking a functional MAO A gene. MAO A-deficient mice differ from wild-type C3H/HeJ (C3H) in terms of showing higher territorial, predatory and isolation-induced aggression. Tg8 demonstrated shorter latencies to cricket killing and to the first attack after 6 weeks isolation than C3H mice. In the resident-intruder paradigm, MAO A-lacking mice were more aggressive than C3H when tested as intruders. In contrast to C3H, attack in Tg8 mice did not depend on different aggressiveness of intruders of BALB/c, A/Sn and C3H strains. Tg8 mice displayed no increase in aggression but demonstrated reduced social investigation towards anesthetized, as well as towards juvenile BALB/c males. Thus, MAO A deficiency in Tg8 mice is accompanied by increased expression of different kinds of aggression, as well as by disruption of normal pattern of social interaction.     

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.     

Activation of intermale aggression by combined estrogen-androgen treatment

Adult CD-1 male mice were gonadectomized and tested for their response to the aggression-promoting property of androgens, estrogens, or combined androgen-estrogen treatment. The results showed that the combined treatment was the most effective, although androgens alone were sufficient for behavioral restoration. These findings suggest that testosterone may activate aggression through both its androgenic and estrogenic metabolites.     

A possible confound and the role of olfaction in mouse aggressive interactions

In investigating the olfactory modulation of aggression in mice, a urine-coating technique frequently has been used. Fighters typically have been tested against castrated animals coated with either urine or water. Then, if the fighters are more aggressive toward urine-coated castrates than toward water-coated castrates, it is concluded that olfaction plays a role in this discriminatory response. However, it is possible that the fighers might react to behavioral differences between these two groups of castrates caused by the different experimental treatment. Three experiments were conducted to study this possible confound and the role of olfaction in the control of agonistic encounters. The results indicated that 1) the confound is not likely to operate; 2) even if the confound is allowed to operate, it is not an effective discriminatory cue; and 3) anosmic fighters do not exhibit differential attacks toward castrates treated with different chemo-signals. Therefore, the emission and perception of olfactory cues do play an important role in mouse agonistic interactions.