Anxiolytic-like activity of SB-205384 in the elevated plus-maze test in mice

Recent studies point to a major role for alpha2-containing GABA-A receptors in modulating anxiety. However, the possible implication of GABA-A receptors containing the alpha3 subunit on anxiety is less known. The aim of this study was to examine the effects of SB-205384 (0.5-4 mg/kg, i.p.), an alpha3 subunit positive modulator of GABA-A receptor, on anxiety tested in the elevated plus-maze in male mice, using classical and ethological parameters. Mice treated with SB-205384 showed an increase in the frequency of entries and the time spent in open arms, as well as a reduction in the time spent in closed arms, as compared with the control group. A notable increase of "head-dipping" unprotected and a reduction of "stretched-attend posture" protected was also evident. These findings indicate that SB-205384 exhibits an anxiolytic-like profile in the elevated plus-maze test, suggesting that GABA-A receptors which contain the alpha3 subunit might be involved in regulation of anxiety.     

Effects of NMDA receptor channel blockade on aggression in isolated male mice

N‐Methyl‐D ‐aspartate (NMDA) receptor antagonists are perspective candidates for medication development for a number of diseases/states that are associated with increased aggressiveness (e.g., opioid withdrawal). The prototypic NMDA receptor antagonist phencyclidine (PCP) itself is a widely abused substance and is known to elevate levels of aggression in drug users. The present study was aimed at testing several drugs that share with PCP the ability to block NMDA receptor–associated channel. The resident‐intruder procedure was used to assess drug effects on aggressive behavior in isolated male mice. Resident aggressive mice were administered NMDA channel blockers (PCP; 0.3–10 mg/kg), dizocilpine (MK‐801; 0.01–0.3 mg/kg), memantine (1–30 mg/kg), and MRZ 2/579 (0.1–5.6 mg/kg). The competitive NMDA receptor antagonist D CPPene (0.1–5.6 mg/kg) was also tested as a compound representing an alternative approach to reduce activity of NMDA receptor complex. PCP, dizocilpine, and memantine inhibited expression of aggressive behaviors only at doses that produced ataxia. The novel channel blocker MRZ 2/579 also produced ataxia at the highest dose level but failed to affect aggressiveness. Reduction in aggression with a corresponding increase in sociability was observed after administration of D ‐CPPene. Overall, the present results suggest that NMDA receptor channel blockers do not exert selective effects on aggressive behavior. Aggr. Behav. 25:381–396, 1999. © 1999 Wiley‐Liss, Inc.     

Behavioral correlates of learned aggression in male mice

The aims of this paper are to study the aggressive behavior in male mice with consecutive experience of victories in 2, 10, and 20 days (T2, T10, and T20 winners) of daily agonistic confrontations under the sensory contact model and to determine the most probable behavioral domains that should be used as animal models for learned aggression in humans. It has been shown that the structure of winners' behavior changes from test to test: the attacking behavior prevailed (81% of the total time) in the behavior of T2 winners. Attacks and diggings (herein: digging up and scattering the litter on the partner' territory) prevailed in the behavior of T10 winners (each approximately 40%). T20 winners demonstrated aggressive grooming half of the testing time and digging behavior 25% of the time. Correlational analysis revealed that the number of significant correlations between the behavioral domains (attacking, digging, aggressive grooming, self‐grooming, threats, rotations) and between different behavioral parameters (latency, number, total and average time) of one behavioral domain are growing from the second test to twentieth test, and the relationships between the behavioral domains change qualitatively. The following may be regarded as elements of learned aggression in male mice: (1) appearance of aggressive grooming instead of the intensive attacking behavior and (2) involvement of the digging behavior in the hostile behavior together with the threats and attacking behavior. Negative correlations between parameters of the behavioral domains may testify to the replacement of one behavioral pattern by another and reflect learned behavior. Positive correlations between certain behavioral domains may reflect the formation of a common motivational background for the winners' behavior. Aggr. Behav. 26:386–400, 2000. © 2000 Wiley‐Liss, Inc.     

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.     

Effects of neonatal cyproterone acetate administration on isolation-induced fighting behavior and mounting behavior in male and female TO strain albino mice

The effects of a single dose (1 mg) of cyproterone acetate administered on either day 1 or day 20 of life on the adult behaviors of male and female TO strain albino mice were studied. The mice were tested both in a “standard opponent”-type situation and in a similar test using a hormonally primed receptive female, after being gonadectomized and maintained with testosterone propionate as adults. Neonatal treatment with this compound had little effect on subsequent fighting behavior in either sex, but clear evidence was produced that this treatment masculinized the sexual behavioral potentialities of the females, an effect which was apparent in animals which had been injected on either day 1 or day 20 of life. Indications were obtained that females treated neonatally with cyproterone acetate were capable of differentiating between the male and female “opponents” in a manner similar to the male. The effects of this treatment on fighting behavior consequently appear to be dissimilar to the effects of neonatal castration in this species. However, the effects on mounting behavior in the females, evidenced in adulthood, seem Likely to be a consequence of the weak androgenic properties of the antiandrogen. The administration of cyproterone acetate neonatally appears to have a more dramatic effect on the adult weights of endocrine organs in females than in mates.     

Effects of female presence on intrasexual aggression in male lizards,Podarcis hispanicus

Resource value and expected gain in reproduction may affect motivation to fight and the likelihood of winning. Previous experiments have showed that males increase their fighting effort when defending a territory that contains females. However, we hypothesized that for an intruding lizard, the value of a new territory may be lower if he already has a female in his own territory, and consequently, aggressivity should be lesser than if he has no access to any female. We staged encounters between males of the lizard Podarcis hispanicus in outdoor terraria to analyze the outcome and detailed behaviors involved in agonistic interactions in the presence or absence of a female in the terraria of resident and intruders. Our results showed that when a female was present, the level of aggressivity of the resident male was higher; the probability of winning the contest also increased, but only if the intruding male had no females in his own terraria. In contrast, when the intruding male was also the owner of another territory containing a female, residents were less aggressive. We suggest that the lack of information on the reproductive state of an unfamiliar female may be enough to decrease fighting motivation of an intruding male, if he has more expectations of success with his own familiar female. We conclude that differences in expected reproductive success with different females may help to decide the outcome of conflicts between males quicker and cheaper. Aggr. Behav. 28:491–498, 2002. © 2002 Wiley‐Liss, Inc.     

Genotype modulates prenatal stress effects on aggression in male and female mice

Prenatal stress (heat and restraint) significantly increased postpartum aggression (proportion of animals fighting and/or the intensity of the behavior) in C57BL/6J female mice and reduced the behavior in DBA/2J females. For intermale aggression, prenatal stress increased the behavior (intensity of aggression) in C57BL/6J males but did not affect aggressive behavior in DBA/2J animals. Infanticidal behavior (the killing of young) exhibited by male mice was not influenced by prenatal stress in either strain. Relative anogenital distance measurements in neonates at birth did not serve as a reliable predictor of strain variation in prenatal stress effects. Prenatal stress did not influence this measure of prenatal androgen exposure in DBA/2J or C57BL/6J females. For males, prenatal stress elevated relative anogenital distance in C57BL/6J mice and decreased this measure in DBA/2J animals. Prenatal stress effects on aggressive behavior in male and female mice therefore depend upon genotype. Strain-dependent differences may be modulated by differences in endocrine reactivity to prenatal stress/and or differential central neural tissue sensitivity to hormones.     

Differential effect of handling on adult aggression in male mice bidirectionally selected for attack latency

Individual variation in intermale aggression is to a significant degree based upon genetic variation, but environmental factors can also exert their influence on the level of aggression. Moreover, genotype–environment interactions are a well‐known phenomenon. In the present experiment, I tested whether cage size or handling during development had an influence on adult attack latency scores. To be able to study a genotype–environment interaction, mice from two bidirectionally on attack latency selected lines were used. The size of the cage in which the mice grew up had no long‐term effect on aggression, neither in the high‐ nor in the low‐aggressive line. Handling, however, significantly increased the adult aggression of males from the low‐aggressive line. Despite the differential effect of handling on genetically high‐ and low‐aggressive mice, handling was not able to undo the marked differences in attack latencies between mice from both lines. Aggr. Behav. 25:365–368, 1999. © 1999 Wiley‐Liss, Inc.     

Effects of serotonin receptor agonists and antagonists on offensive aggression in mice

The effects of serotonin receptor agonists 5-methoxytryptamine and quipazine, and antagonist mianserin on resident-intruder offensive aggression were investigated. Both agonists reduced aggression. The fact that 5-methoxytryptamine preferentially binds to 5-HT-1 receptors strongly suggest that the decreased aggression with S-methoxytryptamine was related to stimulation of an inhibitory 5-HT-1 receptor. It is also suggested that the reduction in aggression with quipazine was related to quipazine's preferential binding to the 5-HT-1 receptor. The 5-HT-2 receptor antagonist mianserin reduced aggression suggesting that 5-HT-2 receptor blockade is inhibitory for aggression. Thus, two serotonin classes of receptors may be differentially involved in offensive aggression.     

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.     

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 ritanserin on offense and defense in male mice

Effects of ritanserin on agonistic behavior of isolated mice exhibiting aggressive or nonaggressive behavioral strategies were studied in pair-wise encounters with group-housed opponents. An ethological approach to behavioral scoring is adopted, which allows for examination of the profiles of individual subjects. Although the data generally support the view that ritanser in has little effect on offense or defense in male mice, the stimulation of pre-aggressive behavior (threats, alerts, tail rattles) was detected in some nonaggressive mice. © 1995 Wiley-Liss, Inc.     

Effects of morphine hydrochloride on social encounters between male mice

The effects of a single injection of morphine hydrochloride (0.3, 0.6, or 1.25 mg/kg) or physiological saline (0.9% NaCI) on the agonistic behaviour elicited by isolation in male mice were examined. Individually housed mice were exposed to anosmic “standard opponents” 30 minutes after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Morphine (at 0.6 and 1.25 mg/kg) significantly and dose-dependently decreased time spent in offensive (“threat” and “attack”) and “digging” behaviours but markedly increased “non-social exploration” without a significant increase of “immobility.” The lowest dose was completely ineffective in producing changes in any of the behaviours studied. It is concluded that these results present a specific ethopharmacological profile characterized by suppression of aggressive behaviour, increase in non-social explotation, and no evident impairment of motor activity. © 1993 Wiley-Liss, Inc.