Behavioral profile of amisulpride in agonistic encounters between male mice

Amisulpride is a substituted benzamide derivative that acts as a selective dopamine D2/D3 receptor antagonist. Although the anti‐aggressive properties of neuroleptic drugs are well known, the effects of amisulpride on agonistic interactions have not been explored, and there are no studies comparing acute and subchronic effects of this compound on aggression in rodents. In this study, we examined the action of amisulpride (5–25 mg/kg, i.p), administered acutely or subchronically for 10 days, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. After acute treatment, amisulpride (5–20 mg/kg) exhibited an ethopharmacological profile characterized by a marked decrease of offensive behaviors (threat and attack) without an impairment of motor activity. By contrast, the anti‐aggressive action of the highest dose used (25 mg/kg) was accompanied by a weak increase of immobility. Body care was also significantly enhanced after treatment with the drug (20 and 25 mg/kg), emphasizing the involvement of dopaminergic receptors in this behavior. After subchronic treatment, no tolerance to amisulpride anti‐aggressive activity was observed. Overall, this behavioral profile is similar to that observed by other atypical neuroleptics. Aggr. Behav. 25:225–232, 1999. © 1999 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 ethanol exposure on juvenile play-fighting and postpubertal aggression in rats

The effects of prenatal ethanol exposure on juvenile play-fighting and postpubertal aggressive behavior in rats were longitudinally assessed in the context of more conventionally applied physical and behavioral measures. Pregnant animals were treated with either 2 gm/kg/day ethanol or isocaloric sucrose over gestation Days 6-19. Reproduction and somatic variables included maternal weight over gestation, offspring weight over Days 1-90, and age at eye opening and incisor eruption. Behavioral variables consisted of negative geotaxis, olfactory discrimination, activity, juvenile play-fighting, and postpubertal aggression. Ethanol offspring had lower birth weights, but there was no significant prenatal treatment effect on subsequent offspring weights or on any other reproductive or somatic variable. Both male and female ethanol-exposed offspring exhibited more play-fighting responses when paired with same-sex controls. Postpubertal aggression levels were assessed in males only. Ethanol-exposed offspring were more aggressive than controls and there was a significant positive correlation between play-fighting and postpubertal aggression ranks. No other behavioral measures discriminated between prenatal treatment groups and none were significantly correlated with either play-fighting or postpubertal aggression rank. The results are consistent with the position that juvenile play-fighting and postpubertal aggression are subserved by common substrates. They also are consistent with predictions derived from the hypothesis concerning a response-inhibition deficit as an effect of prenatal ethanol exposure on behavior.     

The role of body weight in resident-intruder aggression

The behavior of male NIH Swiss mice of various body weights in the resident-intruder test of aggression was investigated. Mice were housed individually for 10 days prior to the test, and allocated to six groups. In the first three groups body weights of residents and group-housed intruders were matched, and the animals were divided into light, average, or heavy groups. In the last three groups weights of the intruder mice were either matched with the residents, or intruders were lighter or heavier than the residents. We found that light residents spent significantly less time in aggressive behaviors and longer time in defensive behaviors than the other two groups. The heavy mice showed most social investigation. The body weights of intruders were also shown to affect the behavior in the test: those residents which had light opponents spent a longer time in aggressive behavior than those which had matched or heavy opponents. The resident mice with heavy opponents showed most defensive behaviors. To study whether pharmacological manipulation may have different effects on behavior in the resident-intruder test in mice having different weights, animals of light, average, and heavy body weight received a low dose (0.8 g/kg) of ethanol 30 min prior to the test. We did not note any effect of ethanol on aggressive behavior in the three groups. The results suggest that body weight plays a significant role in determining the level of aggression and defensive behaviors in the resident-intruder test.     

交往不良同伴对男性未成年犯攻击行为的影响:道德推脱的中介作用

以社会学习理论为基础,运用问卷调查法,通过对368名男性未成年犯的调查,分析了交往不良同伴对攻击行为的影响以及道德推脱在这一影响过程中的中介作用。结果发现:(1)交往不良同伴与男性未成年犯的道德推脱存在显著正相关(γ=0.29, p<0.001),与攻击行为也存在显著正相关 (γ=0.32, p<0.001),同时,道德推脱与攻击行为存在显著正相关 (γ=0.45, p<0.001);(2)交往不良同伴会对男性未成年犯的攻击行为产生显著的正向影响(γ=0.34, p<0.001),道德推脱也会对攻击行为产生显著的正向影响(γ=0.44, p<0.001),同时,道德推脱在交往不良同伴影响攻击行为的过程中发挥着部分中介作用。     

Selective antiaggressive effect of an alpha-2 adrenoceptor agonist naphthylmedetomidine in mice

Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating neurotransmitter release from sympathetic nerves and neurons and play an important role in the regulation of awareness, arousal and vigilance. In our recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced antiaggressive effects in the social conflict test in mice at doses that were twice smaller than those producing sedation. The aim of this study was to ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150-1200 microg/kg i.p.) were studied in the activity cage and in the social conflict tests in mice. Naphthylmedetomidine dose dependently decreased aggressive behavior during social conflict in aggressive mice with significant reduction already at the lowest doses tested (150 microg/kg), whereas locomotion and social investigation were significantly decreased only after four times bigger dose of naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced locomotion in the activity cage significantly only at the highest doses tested (600 and 1200 microg/kg), and this effect was only partially reversed by administration of high doses of an alpha-2 antagonist atipamezole (3 and 10 mg/kg). In nonaggressive mice, the difference between the dose reducing dominant social behavior (social investigation) and locomotion (150 and 300 microg/kg, respectively) was smaller than in aggressive mice. In conclusion, naphthylmedetomidine showed a very strong and selective antiaggressive effect in aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This study suggests that naphthylmedetomidine may have clinical potential as antiaggressive drug.     

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.     

Permanent and transient effects of repeated preweaning stress on social and sexual behaviors of rats

We have reported that exposure of preweaning male and female rats to a model of unpredictable mild physical stressors (Neo-A) can decrease the behavioral and hormonal responses to acute and chronic stress as adults. In this paper we have analyzed the effect of Neo-A on development of social behaviors, including aggressiveness, social dominance, and sexual behavior in adulthood. The subjects were divided into two groups: Neo-A (daily exposed to unpredictable mild stresses- from day 2 up to day 15 of suckling; n = 30 litters) and controls (C) (undisturbed rats, except for testing, during the same period of life; n = 26 litters). When day 6 pups were submitted to a social clustering test the Neo-A group showed a higher rate of litter-mate clustering than C. The 35 days Neo-A males and Neo-A females submitted to a social behavior test after 24 h of social isolation also showed higher scores of time spent in active social interaction than controls, as well as a higher ratio of animals showing aggressive playing. A second social behavior test performed after 48 h of social isolation at days 75-80 of age revealed that only Neo-A females displayed increased social behavior and aggressive behaviors, whereas controls did not. A water competition test performed at 24 and 48 h after water deprivation showed that Neo-A adult males spent more time in possession of the drinking device and drank more frequently than C. When adult proestrous females were exposed to a sexual behavior test, the Neo-A group showed shorter latency and higher scores of lordosis quotient. These results support the view that exposure to this model of repeated mild stress early in life stimulates the development of social behavior, dominance and sexual behavior.     

Chronic sildenafil (Viagra) administration reduces anxiety in intact and castrated male rats

Epidemiological research indicates that sildenafil (Viagra) abuse is associated with increased risk behaviors. The present study employs the open field, a standard animal model used in the field of anxiety research, to examine whether chronic exposure to sildenafil affects anxiety and risk-taking behaviors in gonadally intact and castrated male Wistar rats. Sildenafil (10 mg/kg) or saline were administered three times a week for three weeks. Animals were tested once a week in the open field during and after drug treatment. Sildenafil treatment increased the number of center entries and time spent in the center in intact and castrated animals during and after treatment, suggesting that repeated drug use decreases anxiety. Sildenafil also restored the deficits in exploration and locomotion produced by castration, indicating that sildenafil effects on open field behaviors are independent of endogenous androgens. We caution against generalizing from this study to human behaviors, but propose that the behavioral effects produced by a chronic high dose of sildenafil warrant further studies into its abuse potential.     

Mediating effects of family social support on child psychological adjustment in juvenile rheumatoid arthritis

This study assessed the mediating effects of social support on psychological adjustment in children having to cope with the ongoing chronic strain of juvenile rheumatoid arthritis. Disease activity, family social support, and peer social support were entered into hierarchical multiple regression analyses to statistically predict internalizing and externalizing behavior problems. Family social support was a statistically significant predictor of child psychological adjustment for both internalizing and externalizing behavior problems, accounting for 22% of the variance in each. These findings are consistent with the stress-social support-psychological adjustment relationship that has received empirical attention in studies on physically healthy children. The results are discussed in terms of their implications for primary and secondary prevention efforts for those chronically ill and handicapped children who are at increased risk for psychological adjustment problems.     

Differential sensitivity to the effects of nicotine and bupropion in adolescent and adult male OF1 mice during social interaction tests

Few studies have compared the action of both nicotine (NIC) and bupropion (BUP), an antidepressant used to treat NIC dependence, on social and aggressive behavior at different ages. This study aims to determine whether these drugs produce differential effects in adolescent (postnatal day: 36-37) and adult (postnatal day: 65-66) mice that have been housed individually for 2 weeks in order to induce aggressive behavior. Mice received BUP (40, 20, or 10 mg/kg), NIC (1, 0.5, and 0.25 mg/kg as base), or vehicle earlier to a social interaction test. BUP (40 mg/kg) decreased social investigation and increased nonsocial exploration in both adolescent and adult mice. The same effects were also observed in adult mice administered with a lower dose of the same drug (20 mg/kg). In adolescents, NIC (1 mg/kg) decreased social investigation, but this effect did not reach statistical significance in adults. In conclusion, a differential sensitivity to the effects of NIC or BUP emerged in some of the behavioral categories when the two age groups were compared.     

睾酮素与反社会倾向未成年犯的攻击行为：敌意注意偏向的中介和皮质醇的调节作用

为考察睾酮素与反社会倾向未成年犯攻击行为的关系,在整合攻击行为生物激素视角和社会认知视角的基础上,探究敌意注意偏向的中介作用与皮质醇的调节作用。对84名未成年犯的激素水平、敌意注意偏向以及攻击行为进行调查。结果显示：(1)敌意注意偏向(注意不稳定性、注意回避)在睾酮素对攻击行为的影响中起完全中介作用;(2)皮质醇调节睾酮素与敌意注意偏向的关系,仅在高皮质醇水平下,敌意注意偏向的中介效应显著。基于生物激素影响攻击行为的中介机制和调节机制,可尝试从增加对敌意刺激的注意回避和提高皮质醇水平两个方面对反社会倾向未成年犯的攻击暴力行为进行干预。     

The effects of naloxone and cage size on social play and activity in isolated young rats

The effects of large and small housing environments as well as naloxone on social play (as defined by pinning behavior) in isolated postweanling male rats were investigated. Animals housed in small cages played significantly more than those housed in larger cages. This effect was not observed when cage size was reversed. Administration of 0.5, 1.0, and 5.0 mg/kg of naloxone resulted in significant decreases in play behavior as compared to saline controls, both before housing environments were switched, and after. Animals in both isolation conditions were also compared to animals that were socially housed. Isolation was found to increase social play as well as the time spent in active social interaction, but had no effect on locomotor activity. While housing in a small cage increases play behavior, it had no effect on the amount of time spent in active social interaction or on activity. While administration of 0.5, 1.0, and 5.0 mg/kg naloxone to habituated animals differentially housed did not result in an overall decrease in activity, when compared with saline controls, only those animals housed in small cages and injected with the high dose of naloxone differed significantly from controls. In animals having no prior play experience, the activity of animals housed in the large and small cages differed significantly from each other only in the saline and 5.0 mg/kg naloxone conditions. Since naloxone's effect on play behavior was strong, but its effect on activity was not profound, our data suggest that naloxone primarily affects the affective component of play rather than altering activity levels.     

Effects of peripheral immune activation on social behavior and adrenocortical activity in aggressive mice: Genotype-environment interactions

To explore genetic-developmental differences in the biobehavioral effects of induced illness, males from two lines of mice selectively bred for high or low levels of aggressive behavior were injected with endotoxin (Escherichia coli, LPS: 0.25 mg/kg, 1.25 mg/kg, or 2.5 mg, i.p.) or saline. Body temperature, weight, and locomotor activity were monitored immediately before and 8 and 24 hr after injection. Twenty-four hours after injection, social behaviors were assessed in a 10-min dyadic test, and hypothalamus, spleen, and serum were collected. In both lines, endotoxin treatment increased behavioral immobility ("freezing") and decreased social exploration. Other effects showed line differences: Males from the high-aggressive line had a lower threshold to endotoxin-induced effects on body temperature, weight loss, spleen weight, and corticosterone. Social reactivity (startle response to mild social investigation) increased in the high-aggressive line and decreased in the low-aggressive line after treatment. In the high-aggressive line only, endotoxin decreased attack frequency and increased latency to attack. The interactions between selected line (genotype) and endotoxin treatment (environment) demonstrate that genetic-developmental differences in social and aggressive behavior may indicate the extent to which immune stimuli (e.g., bacteria, viruses, cytokines) function as "biobehavioral stressors." Aggr. Behav. 23:93–105, 1997.© 1997 Wiley-Liss, Inc.     

The effect of a self-monitored relaxation breathing exercise on male adolescent aggressive behavior

This study sought to contribute to the identification of effective interventions in the area of male adolescent aggressive behavior. Existing research includes both group- and single-case studies implementing treatments which typically include an anger-management component and its attendant relaxation and stress-reduction techniques. The design of this study was single-subject with multiple baselines across 6 subjects on 2 behavioral measures. The setting was a residential juvenile justice program for male adolescents, and the treatment was a relaxation breathing exercise. The results of the study were mixed, with improvement on both behavioral measures in 2 of the 6 participants.     

Video games and aggressive thoughts, feelings, and behavior in the laboratory and in life

Two studies examined violent video game effects on aggression-related variables. Study 1 found that real-life violent video game play was positively related to aggressive behavior and delinquency. The relation was stronger for individuals who are characteristically aggressive and for men. Academic achievement was negatively related to overall amount of time spent playing video games. In Study 2, laboratory exposure to a graphically violent video game increased aggressive thoughts and behavior. In both studies, men had a more hostile view of the world than did women. The results from both studies are consistent with the General Affective Aggression Model, which predicts that exposure to violent video games will increase aggressive behavior in both the short term (e.g., laboratory aggression) and the long term (e.g., delinquency).     

Comparison between BALB/cJ and BALB/cByJ mice in tests of social behavior and resident-intruder aggression

The behavior of male mice from two BALB strains, the BALB/cJ strain and the BALB/cByJ strain, was examined with a social behavior test and a resident-intruder paradigm. Prior to testing, the animals were isolated for 0, 2, 5, or 10 days. In the social behavior test the pairs of BALB/cJ mice spent more time in active social interaction than pairs of BALB/cByJ mice, although the latter strain showed more locomotor activity. BALB/cJ mice isolated for 5–10 days, when tested in a familiar environment were more aggressive than mice from the BALB/cByJ strain. In the resident-intruder paradigm, in which a resident BALB mouse was confronted with an intruder NIH Swiss mouse, the BALB/cByJ mice showed more social investigation in their home cage towards the intruders, but there were no significant differences between the two strains in the amounts of aggressive behavior exhibited. The results of these experiments suggest that there are some differences in the social behavior of the genetically related BALB/cJ and BALB/cByJ mice. However, the differences appear subtle and paradigm-specific.     

Effects of medial preoptic-anterior hypothalamic lesions on development of sociosexual behavior in dogs

Bilateral medial preoptic-anterior hypothalamic lesions in adult male dogs eliminate or impair copulatory behavior and reduce urine-marking responses but do not affect aggressive behavior. The present study examined the emergence of the adult forms of these same male sociosexual behavioral patterns when the lesions are made prior to puberty. The subjects were allowed to interact with male peers during development. Animals with lesions had reduced frequence of juvenile mounting and an almost total absence of male copulatory activity in adulthood. Urine-marking and aggressive behavior in the juvenile and adult periods were not affected by the lesions. The findings reveal a sparing of function with regard to urine-marking but not sexual behavior.     

Effects of chronic administration with high doses of testosterone propionate on behavioral and physiological parameters in mice with differing basal aggressiveness

The effects of testosterone propionate, an anabolic‐androgenic steroid, on the behavior displayed during a social encounter by gonadally intact male mice were investigated. Animals were distributed into three groups according to their attack latency in a pre‐screening test (high‐, moderate‐, and low‐ attacking mice) and each group received weekly injections of 60 or 120 mg/kg of testosterone or sesame oil for 10 weeks. Behavioral tests were then carried out. Afterwards, organs were weighed and blood samples collected in order to obtain hormonal data. Treatment had a differential impact on attack in the three groups of animals. Only the high‐attacking testosterone‐treated mice showed lower total duration of attack than their controls. Those that received 60 mg/kg spent more time exhibiting exploratory behaviors. As an index of the anabolic activity of the drug, all testosterone‐treated mice had heavier kidneys and, as an index of the androgenic activity of testosterone propionate, they had heavier seminal vesicles, lighter testes, and showed higher testosterone levels in a dose‐dependent way than their controls. Hence, the effect of treatment on peripheral physiological parameters was similar in all three groups whereas behavioral effects differed depending on basal aggressiveness, considered a characteristic of coping style. Aggr. Behav. 29:173–189, 2003. © 2003 Wiley‐Liss, Inc.     

未成年人归因的内隐特征与攻击行为

本研究使用投射法这一内隐社会认知的研究方法,考察了朱成年人罪犯群体与正常群体的攻击行为内隐社会认知过程的特征,结果表明：整体上而言,未成年人罪犯群体与正常群体的内隐归因方式存在显著差异,罪犯的内控程度要低于常人的内控程度。从而得出罪犯产生攻击性犯罪行为的原因之一是他们的归因存在偏差,支持了攻击行为成因的归因模型。未成年人男女两性在内隐的内外控方面不存在显著差异,且结果提示归因方式与女性罪犯的攻击行为没有必然联系。