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PubMed1986

Differential effects of ethyl (R,S)-nipecotate on the behaviors of highly and minimally aggressive female golden hamsters.

The GABA uptake inhibitor ethyl (R,S)-nipecotate produces a dose-dependent suppression of aggression in highly aggressive hamsters but not in minimally aggressive ones. This suppression occurs at doses below those producing peripheral cholinergic effects; at the highest dose used it persists after these effects have dissipated. Doses sufficient to suppress aggression have no significant effect on grooming, locomotor activity and other behaviors but do affect sunflower seed acceptance. The differential effects of the drug on highly and minimally aggressive animals may indicate that their differences in aggression are due to differences in endogenous GABAergic activity. These results, together with previous evidence for parallel circadian variation in GABA uptake and aggressive behavior, suggest that GABA uptake may be an important endogenous regulator of aggression.

Aggression↗
PubMed2002

Reduced aggression in mice lacking the serotonin transporter.

RATIONALE: Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. OBJECTIVES: To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage activity and 5-HT(1A/1B) receptor function in 5-HTT KO mice as factors contributing to an aggressive phenotype. METHODS: Isolated male 5-HTT KO mice were compared to +/+ control mice using the resident-intruder test for aggression over two encounters. Locomotor activity was measured in the home cage over a 24-h period. 5-HT(1A/1B) receptor function was assessed via the pharmacological effects of the 5-HT(1A/1B) receptor agonist, RU24969, on locomotion. RESULTS: 5-HTT -/- mice were slower to attack the intruder and attacked with less frequency than +/+ littermates, but showed equivalent social investigation. 5-HTT +/- mice were as quick to attack, but made fewer overall attacks, as compared to +/+ controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/- and +/+ mice, but not in 5-HTT -/- mice. 5-HTT -/- mice showed a normal circadian pattern of home cage activity, but less activity overall, as compared to 5-HTT +/- and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/- and +/+, but not 5-HTT -/- mice. CONCLUSIONS: Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT(1A/1B) receptor function may contribute to reduced aggression in 5-HTT KO mice.

Aggression↗
PubMed2003

GABAA/alpha1 receptor agonists and antagonists: effects on species-typical and heightened aggressive behavior after alcohol self-administration in mice.

RATIONALE: The positive modulation of gamma-aminobutyric acid type-A (GABAA) receptors is a putative mechanism via which alcohol escalates aggressive behavior. Broad-spectrum benzodiazepine antagonists block alcohol-heightened aggression in rats and monkeys. However, the degree to which GABAA subunit composition plays a role in heightened aggressive behavior induced by self-administration of a moderate alcohol dose remains unresolved. OBJECTIVE: Beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) and zolpidem act preferentially at GABAA receptors containing the alpha1 subunit as antagonist and agonist, respectively, and serve as useful tools to evaluate the role of GABAA receptor subtypes in self-administered alcohol on aggression. METHODS: Male resident mice, housed in breeding pairs, were conditioned to nose-poke in a removable panel in their home cage, with each fifth poke being reinforced by the delivery of 0.05 ml of 6% ethanol (EtOH). After consuming EtOH, the resident mice were given the antagonists beta-CCt and flumazenil or agonists zolpidem and triazolam, and then confronted an intruder male in their home cage for a 5-min period. RESULTS: Following self-administration of EtOH (1.0 g/kg, 1.7 g/kg), 14 of 37 resident mice displayed unusually large increases in the frequency of attack bites and sideways threats. Flumazenil or beta-CCt decreased alcohol-heightened and non-heightened aggression in a dose-dependent manner. Administration of 3 mg/kg beta-CCt lowered the aggression-heightening effects of 1 g/kg and 1.7 g/kg EtOH, but did not antagonize the sedative effects of 3.0 g/kg EtOH. Triazolam and zolpidem decreased alcohol-heightened and non-heightened aggressive behavior, and these antiaggressive effects were accompanied by reduced motor activity, indicating sedation. CONCLUSIONS: Benzodiazepine antagonists, particularly those acting preferentially at GABAA/alpha1 subunit-containing receptors, decrease alcohol-heightened and species-typical aggressive behavior, but are ineffective in attenuating the sedative effects of alcohol.

Aggression↗
PubMed2006

5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice.

RATIONALE: Systemic injections of 5-HT(1B) receptor agonists have been shown to have specific anti-aggressive effects in aggressive individuals. One site of action for these drugs is the 5-HT(1B) receptors in the ventral orbitofrontal cortex (VO PFC), an area that has been implicated in the inhibitory control of behavior and is a terminal region for 5-HT projections. OBJECTIVE: To assess the anti-aggressive effects of the 5-HT(1B) receptor agonist CP-94,253 when microinjected into the VO PFC (0.1, 0.56, and 1.0 microg/0.2 microl) or into the infralimbic prefrontal cortex (IL PFC; 1.0 microg/0.2 microl) in separate groups of aggressive resident male mice. To confirm the 5-HT(1B) receptor as the critical site of action for the anti-aggressive effects, the 5-HT(1B/D) antagonist GR-127,935 was microinjected at 10.0 microg/0.2 microl into the VO PFC. After recovery from surgery, the anti-aggressive effects of microinjected CP-94,253 were studied during 5-min resident-intruder confrontations that were recorded and analyzed. RESULTS: Microinjections of CP-94,253 (0.56 and 1.0 microg/0.2 microl) dose-dependently reduced the frequency of attack bites and sideways threats. This effect was behaviorally specific because non-aggressive motor activities were not significantly altered by the drug. In the IL vmPFC or in an area lateral to the VO PFC, CP-94,253 (1.0 microg/0.2 microl) did not have significant behavioral effects. CONCLUSIONS: The results highlight the 5-HT(1B) receptors in the VO PFC as a particularly important site for the inhibition of species-typical aggressive behavior in male mice.

Aggression↗
PubMed2003

Self-rated aggression and cerebral monoaminergic turnover. Sex differences in patients with persistent depressive disorder.

OBJECTIVE: Outward-directed violence and impulsivity in humans and primates has frequently been related to abnormal brain monoaminergic turnover. Self-rated aggression is likely to be clinically relevant,and its psychobiological basis needs investigation. SUBJECTS: Sixty-six patients (40 women and 26 men) with persistent depressive disorder (PDD) were compared with 497 control subjects from the general Swedish population. METHODS: We administered the Aggression Questionnaire - Revised Swedish Version (AQ-RSV) to patients and control subjects. In patients, CSF 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-5-hydroxyphenylglycol (MHPG) in CSF were analyzed. Total Aggression score and Aggression subfactors 'Physical Aggression','Verbal Aggression','Anger', and 'Hostility'were correlated with CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA),and 3-methoxy-5-hydroxyphenylglycol (MHPG). RESULTS: Overall, Hostility was positively related to CSF MHPG (t=2.27, p=0.015). Split by sex,Hostility was related with 5-HIAA in males (r=0.62,p=0.003),and with MHPG in females (r=0.38, p=0.03). Comparing self rated aggression with age- and sex-matched data from the general Swedish population, the most prominent deviation was increased Hostility score among PDD patients. Among patients, all aggression factors were nominally higher in women than in men, with the most pronounced sex difference in Hostility (t=-1.89, p=0.04). CONCLUSIONS: Results suggest a clinically meaningful sex difference in a positive relationship between hostility and serotonergic/noradrenergic turnover in PDD patients.

Adult↗
PubMed2005

Reactive and proactive aggression in children--a review of theory, findings and the relevance for child and adolescent psychiatry.

The clinical population of aggressive children diagnosed as having an oppositional defiant disorder (ODD) or a conduct disorder (CD) is heterogeneous, both with respect to behaviour and aetiology. Recently, the following distinction has been proposed that might further clarify this heterogeneity: reactive aggression is an aggressive response to a perceived threat or provocation, whereas proactive aggression is defined as behaviour that anticipates a reward. In this article we examine various aspects of this distinction. We will [1] examine the evidence that reactive and proactive aggression are distinct phenomena by discussing the theories underlying the distinction between the subtypes in humans and we briefly review evidence for a similar distinction in animals; [2] we critically review the literature on the measurement in children via questionnaires and behavioural observations; we then point out that the correlation observed between the subtypes is due to the fact that many children show both types of aggression; [3] we review the literature on specific characteristics of the subtypes giving attention to social information processing, peer status, biological correlates and developmental history, and demonstrate that there is some evidence to suggest that reactive and proactive aggression are distinct dimensions; [4] we discuss the relevance of the distinction between reactive and proactive aggression for child and adolescent psychiatry.

Adolescent↗
PubMed2006

Melanocortin-5 receptor deficiency in mice blocks a novel pathway influencing pheromone-induced aggression.

The rodent preputial gland secretes aggression-promoting pheromones and expresses melanocortin-5 receptor (MC5R), but the functional relationship is poorly understood. We investigated whether MC5R deficiency in male mice alters stimulatory melanocortin influences on preputial growth and pheromone-induced aggression. In wild-type (MC5R(+/+)) pairs, repeated NDP-MSH injection decreased attack latency and increased aggression in initial attackers. Similar NDP-MSH treatment in MC5R-deficient (MC5R(-/-)) pairs failed to alter attack latency or aggression frequency, but aggression increased in vehicle-injected opponents. NDP-MSH treatment promoted preputial hypertrophy, and in MC5R(+/+) mice paired against non-aggressive stimulus opponents it decreased attack latency and increased aggression. MC5R(-/-) mice were insensitive to behavioral and physiological effects of NDP-MSH, and preputialectomized mice were insensitive to behavioral effects of NDP-MSH. The results suggest that MC5R inactivation reduced a pheromonal signal for aggression that acts on donors, rather than their opponents.

Aggression↗
PubMed2005

Proximal peer-level effects of a small-group selected prevention on aggression in elementary school children: an investigation of the peer contagion hypothesis.

Examined peer contagion in small group, selected prevention programming over one school year. Participants were boys and girls in grades 3 (46 groups, 285 students) and 6 (36 groups, 219 students) attending school in low-resource, inner city communities or moderate resource urban communities. Three-level hierarchical linear modeling (observations within individuals within groups) indicated that individual change in aggression over time related to the average aggression of others in the intervention group. The individual child was "pulled" toward peers' mean level of aggression; so the intervention appeared to reduce aggression for those high on aggression, and to make those low on aggression more aggressive. Effects appeared to be magnified in either direction when the child was more discrepant from his or her peers. From these results we derive a principle of "discrepancy-proportional peer-influence" for small group intervention, and discuss the implications of this for aggregating aggressive children in small group programs.

Aggression↗
PubMed2005

Diet-related modification of cuticular hydrocarbon profiles of the Argentine ant, Linepithema humile, diminishes intercolony aggression.

Territorial boundaries between conspecific social insect colonies are maintained through a highly developed nestmate recognition system modulated by heritable and, in some instances, nonheritable cues. Argentine ants, Linepithema humile, use both genetic and environmentally derived cues to discriminate nestmates from nonnestmates. We explored the possibility that intraspecific aggression in the Argentine ant might diminish when colonies shared a common diet. After segregating recently field-collected colony pairs into high or moderate aggression categories, we examined the effect of one of three diets: two hydrocarbon-rich insect prey, Blattella germanica and Supella longipalpa, and an artificial (insect-free) diet, on the magnitude of aggression loss. Aggression diminished between colony pairs that were initially moderately aggressive. However, initially highly aggressive colony pairs maintained high levels of injurious aggression throughout the study, independent of diet type. Each diet altered the cuticular hydrocarbon profile by contributing unique, diet-specific cues. We suggest that acquisition of common exogenous nestmate recognition cues from shared food sources may diminish aggression and promote fusion in neighboring colonies of the Argentine ant.

Aggression↗
PubMed2005

Social isolation, impulsivity and depression as predictors of aggression in a psychiatric inpatient population.

Aggressive behavior among psychiatric inpatients remains an issue of concern for staff, families and patients themselves. At the present time, studies examining prediction of aggression among psychiatric inpatients have focused mainly on diagnostic or demographic risk factors. Unfortunately little is known about specific social functioning and personality risk factors that may help identify specific individuals at risk for aggressive behavior. Given that many individuals who have engaged in violent criminal behavior have been observed to experience a combination of social isolation, depression and impulsiveness, it is possible that this same combination of traits may function as a predictor of aggression among psychiatric inpatients. The current study examines whether psychiatric inpatients with a combination of social isolation, depression and impulsivity are significantly more likely to become aggressive than other psychiatric inpatients without that combination of factors. Results indicated that impulsivity functioned as a positive predictor of aggression, whereas depression acted as a protective factor. Perceived social support did not appear to relate strongly to aggression. Further, physicians' ratings of hostility were more predictive of aggressive incidents than were self-reports of hostility. Clinical implications of these findings are discussed.

Adult↗
PubMed1994

Childhood depression and aggression: a covariance structure analysis.

The purpose of the present study was to: (a) evaluate the comorbidity of depression and aggression in a community sample of school-age children; (b) demonstrate the use of confirmatory factor analysis as a statistical tool in the assessment of the construct validity of childhood depression and aggression measures; and (c) using multisample analysis and structural equation modeling, examine the generalizability of comorbidity across two potential moderating or mediating variables (i.e. gender and peer unpopularity). A series of hypothetical models was tested to identify the number of factors represented by the data, the convergent and discriminant validity of the measures, the relationship between the latent variables of childhood depression and aggression, the influence of method-specific variation, and structural relationships among the latent constructs. Results supported a two-factor comorbidity model (childhood depression and aggression) and the presence of method effects (i.e. rater bias). Though the basic measurement model identified substantial comorbid symptoms and was generally invariant across gender, boys' self-reports of symptomatology evidenced poor validity. The structural equation models supported the independent effects of peer aggression and unpopularity on depression for both boys and girls, though aggression may be somewhat more strongly related to unpopularity among girls. Results were consistent with psychiatric investigations of comorbid depressive and aggressive disorders and emerging developmental psychopathology research on the socioemotional development of aggression and depression in youth.

Adolescent↗
PubMed1989

EEG and brainstem auditory evoked response potentials in adult male drug abusers with self-reported histories of aggressive behavior.

Auditory brainstem evoked response (BAER) and spontaneous electroencephalogram (EEG) were measured in 124 adult male drug abusers. We examined the relationships among psychiatric diagnoses, paper and pencil measures of aggression and hostility, and electrophysiological features. Subjects meeting criteria for antisocial personality disorder (ASP), as defined by DSM-III, were not significantly different from non-ASP subjects for either BAER or spontaneous EEG measures. The more overtly aggressive subjects had significant delays in BAER latency. Aggressive subjects also had more delta activity and less alpha activity in the spontaneous EEG, as have been observed in "psychopaths" and "criminals." Although ASP and aggression are related, these data indicate that aggressiveness may be a separate, albeit overlapping, trait. As both early aggression and a diagnosis of ASP are predictors of later drug use, the findings that only aggression was associated with EEG slowing and brainstem delays may indicate that ASP and aggression make independent contributions to vulnerability to the development of drug abuse.

Adult↗
PubMed1988

Differential hormonal control of aggression and sexual behavior in female Syrian hamsters.

These experiments were designed to test the effects of chronic estradiol treatment on aggression and sexual behavior in female hamsters. Isolated female hamsters were ovariectomized and tested for their behavioral responses to a group-housed, ovariectomized female hamster (aggression test) and a group-housed, intact male hamster (sexual behavior test). Following these baseline tests, the experimental females were implanted sc with Silastic capsules containing different concentrations of estradiol (100, 25, 10, or 0%) diluted with cholesterol and retested 3, 7, 10, and 14 days after implantation. High levels of aggression were observed on the baseline test, with no changes in aggression toward an intruder female observed for any implant group on subsequent tests. Despite these high levels of aggression toward another female, most of the estradiol-treated females (80% at 14 days) were sexually responsive in the presence of a male. There was no effect of Silastic estradiol concentration on sexual behavior, even though a range of serum estradiol levels (39-105 pg/ml) resulted. Lordosis latencies decreased and lordosis durations increased over the extent of estradiol treatment. Seventeen days after Silastic implantation, all females were injected with progesterone and restested. Estradiol-treated females showed an extreme reduction in aggression toward a stimulus female, as well as a further stimulation of sexual behavior after progesterone treatment. High levels of aggression in cholesterol-treated females (0% estradiol) were maintained even after progesterone injection, and these females never displayed any sexual responsivity. These results suggest that sexual behavior in the female hamster is sensitive to estradiol alone, whereas the inhibition of aggression requires the combination of estradiol plus progesterone.

Aggression↗
PubMed1988

Control of aggression and dominance in white-throated sparrows by testosterone and its metabolites.

In three experiments, we investigated whether testosterone itself or its metabolites activate aggression and dominance in white-throated sparrows Zonotrichia albicollis. Groups of five to six sparrows, each treated with a different steroid implanted subcutaneously, were observed in outdoor aviaries during late winter to determine the birds' rates of aggression (supplantations and attacks scaled to the number of available subordinates) and dominance rankings with opponents not previously encountered. In Experiment 1, testosterone (T) had a greater effect on aggression and dominance than did androstenedione, 5 alpha-dihydrotestosterone (D), androsterone, or estradiol (E). In Experiment 2, birds with T or D + E had higher aggression scores and dominance ranks than birds with either D or E alone. Birds with T and D + E did not differ. The testosterone metabolites, D and E, thus acted synergistically to determine rates of aggression and dominance ranks. To corroborate these results, in Experiment 3 we treated T-implanted birds with the following blocking agents: ATD, expected to reduce conversion of T to E (AT birds); progesterone, expected to reduce conversion of T to D (PT birds); or both (APT birds). The APT birds had lower aggression scores and dominance ranks than did AT or PT birds, despite having higher mean levels of circulating T than AT or PT birds or birds implanted with T alone. Cyproterone acetate also reduced aggression scores and dominance in T-implanted birds. We conclude that the hormonal control of aggression and dominance in these birds requires conversion of testosterone to both androgenic and estrogenic metabolites.

Aggression↗
PubMed1990

Prolonged estrogen-progesterone treatment of nonpregnant ovariectomized rats: factors stimulating home-cage and maternal aggression and short-latency maternal behavior.

A 16-day treatment of nonpregnant, ovariectomized rats using 5-mm Silastic implants of estradiol (E), daily injections of 4 mg of progesterone (P), and terminal injections of 5 micrograms/kg of estradiol benzoate (EB) to provide a pregnancy-like pattern of hormone exposure, stimulates (a) home-cage aggression toward unfamiliar intruder rats, (b) short-latency maternal behavior when the females are exposed continuously to pups, and (c) maternal aggression after maternal care has been initiated. Preliminary experiments examined the persistence of stimulation of aggression by the 16-day treatment in the absence of exposure to pups eliciting maternal care, and whether an abbreviated, 1-week treatment stimulates aggression equally. Subsequent experiments examined the importance of the elements of the treatment (E implants, P injections, EB injection), and whether prolonging exposure to P or E would alter its behavioral effects. The full 16-day E/P/EB treatment stimulated higher levels of home-cage and maternal aggression, and shorter maternal behavior latencies than abbreviated and partial treatments. E in combination with P or EB significantly raised home-cage aggression, whereas P alone was without effect. Administering P for 2 additional days attenuated reductions in maternal behavior latencies by E/P/EB, but did not reduce home-cage or maternal aggressiveness. Continuous exposure to E throughout testing did not affect any dependent variable. Comparing these findings to earlier data and reports suggests that hormone exposure for 2 weeks or more, and provision of P levels approaching those of pregnancy are important to the effects of the E/P/EB treatment on aggression.

Aggression↗
PubMed1986

Testosterone removal in rats results in a decrease in social aggression and a loss of social dominance.

Alpha male rats from mixed sex colony groups were tested for aggressiveness toward nonaggressive male intruders. Afterward, they were castrated and implanted with testosterone filled Silastic tubes, castrated and implanted with empty tubes, or sham castrated and implanted with empty tubes. There were significant declines in the aggressiveness (lateral attacks, bites, and piloerection but not on-top) of castrated rats without testosterone replacement but not in castrated rats with testosterone replacement. At a second operation, castrated animals had their testosterone capsules removed or had their empty capsules replaced with testosterone filled capsules. When tested for aggression toward nonaggressive intruders, those alpha males which had testosterone removed declined in aggressiveness while those which had it implanted returned to a level of aggressiveness close to that emitted by sham castrated control animals. Subordinate males became dominant when alpha males were castrated and not given testosterone replacement. In a final series of observations, sham castrated males were found to be more aggressive than castrated males when pitted against one another. It is argued that testosterone plays a primary role in intermale social aggression and that the decline in aggressiveness following castration is typically accompanied by a loss of social dominance.

Aggression↗
PubMed1986

Ultrasonic vocalizations and aggressive behavior in male rats.

The aim of the present study was to know whether 22-28-kHz vocalizations have any communicatory role in the regulation of aggressive behavior in male rats of the Wistar strain. In pairs of intact rats 22-28-kHz vocalizations showed a positive correlation with the extent of aggressive behavior. The pattern of aggressive behavior during ultrasonic vocalizations was different from that just before and just after the vocalizations. However, surgically deafened rats were less active in aggressive behavior and more active in ambulatory activity in the open field than the controls. Muted rats were not different from the controls in both aggressive behavior and ambulatory activity. The present result that the deprivation of ultrasonic signals failed to increase aggressive behavior does not support the classical hypothesis that ultrasonic vocalizations inhibit the initiation of aggressive behavior. It is concluded that ultrasounds emitted during aggressive encounters may have little communicative value in male rats.

Aggression↗
PubMed1987

Intermale social aggression: reinstatement in castrated rats by implants of testosterone propionate in the medial hypothalamus.

Male hooded rats were castrated, subcutaneously implanted with testosterone-filled silastic tubes, and individually housed with an intact adult female rat. An unfamiliar male intruder was introduced into each colony on a weekly basis and the aggressive behavior of the resident male was recorded. When the intermale social aggressive behavior of the resident male toward the intruder reached a high level in terms of a composite aggression score, the subcutaneous testosterone tubes were removed. Weekly tests of aggression toward unfamiliar intruders continued until the aggression of the resident male dropped to a low level for two successive weeks in terms of our composite aggression score. Bilateral implants of pellets of testosterone propionate were then made into the medial hypothalamus or adjacent tissue. A control group was implanted with cholesterol pellets into the medial hypothalamus. During four weekly tests following the implant, rats with testosterone propionate implants in the medial hypothalamus showed increases in lateral attacks, lateral attack duration, bites, and piloerection. The increase in aggression was not consistently displayed by animals with testosterone propionate implants dorsal or anterior to the medial hypothalamus or by animals with cholesterol implants in the medial hypothalamus. These results suggest that the medial hypothalamus or closely adjacent tissue contains testosterone-sensitive neural circuitry modulating intermale social aggression.

Aggression↗