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Sex differences and developmental effects of oxytocin on aggression and social behavior in prairie voles (Microtus ochrogaster).

Various hormones, including sex steroids and neuropeptides, have been implicated in aggression. In this study we examined (1) sex differences in intrasexual aggression in naïve prairie voles; (2) the effects of developmental manipulations of oxytocin on intrasexual aggression; and (3) changes in patterns of intrasexual aggression after brief exposure to an animal of the opposite sex. Within 24 h of birth, infants were randomly assigned to receive either an injection of oxytocin (OT) or oxytocin antagonist (OTA) or to one of two control (CTL) groups receiving either isotonic saline or handling without injection. As adults, animals were tested twice in a neutral arena; before (Test 1) and 24 h after (Test 2) a 4-h exposure to an animal of the opposite sex. In Test 1, CTL males were more likely to show aggressive and less likely to show social behavior than CTL females. No significant treatment differences were observed within either sex in Test 1. In Test 2, after brief exposure to a male, females treated with OT became more aggressive and less social than OTA or CTL females. Male aggressive behavior did not change after exposure to a female. An increase in aggression and decline in social behavior toward other females, seen here in OT-treated females, is typically observed only following several days of female-male cohabitation. These findings demonstrate a sex difference in intrasexual aggression and suggest that neonatal exposure to OT may facilitate the onset of the mate-guarding component of pair bonding in female prairie voles.

Aggression↗

Social factors regulate female-female aggression and affiliation in prairie voles.

Although patterns of aggression and affiliation may play a major role in social organization, the mechanisms underlying these behaviors are not well understood. The purpose of this study was to examine the effects of social and hormonal experience on female-female aggression and affiliation in prairie voles, Microtus ochrogaster. Prairie voles exhibit the traits of social monogamy and tend to live in communal families structured around a male-female pair. It is rare for two unrelated females within a family to successfully reproduce. In this study, the social and/or hormonal experiences of female prairie voles were varied and female-female aggression and affiliation were measured during dyadic encounters with unfamiliar, nonaggressive females. An increase in aggression and decline in affiliative behaviors toward a stimulus female was observed during pregnancy and following male-cohabitation, with or without mating. Pairing with another female did not result in changes in either aggressive or affiliative behaviors toward the stimulus female. Female-female aggression increased and affiliative behaviors declined, with a maximal effect following approximately 8-12 days of male cohabitation. Similar patterns of change were seen in both ovariectomized and gonadally intact females, and treatment with estradiol and subsequent sexual experience did not significantly alter the tendency of females to show aggression or affiliative contact. Social experiences associated with prolonged cohabitation with a male facilitate the induction of female-female aggression; however, ovarian hormones, pregnancy or mating are not essential to induce aggression.

Aggression↗

Castration does not inhibit aggressive behavior in adult male prairie voles (Microtus ochrogaster).

The relationship between castration and reduced male aggression is well established. However, anecdotal observations of male prairie voles (Microtus ochrogaster) suggest that castration does not reduce aggressive behavior. To investigate the role of testicular androgens on aggressive behavior, castrated or gonadally intact male prairie voles were paired in a neutral arena with a gonadally intact vole. Castration did not reduce the frequency of intermale aggression. In Experiment 2, aggressive behavior was examined further using resident-intruder, grouped aggression, and aggression against a lactating female models. Again, castration did not affect the frequency of aggression in male prairie voles. Taken together, the results of this study suggest that aggressive behavior may be independent of gonadal steroid hormones in adult male prairie voles.

Aggression↗

Effects of testosterone on aggressive behaviour after social mixing in male lambs.

The aim of this article was to study the effects of testosterone administration on the aggressive behaviour of male prepubertal lambs after mixing unacquainted individuals. Forty male lambs from two different flocks (1 and 2), 20-22 kg body weight and 10-12 weeks old, were distributed into four groups: C1 and C2 (control groups), and T1 and T2 (testosterone-treated groups). Groups C1 and T1 came from flock 1, while groups C2 and T2 came from flock 2. Animals in groups T1 and T2 were given 250 mg of testosterone enantate intramuscularly on the first experimental day. Animals from the same flock were kept as a group during the first 15 days; on Day 16, control animals (C1 and C2) were moved into one pen and testosterone-treated animals (T1 and T2) into another one, where they were kept for 3 additional days. Aggressive interactions and hormone plasma levels were recorded both before and after social mixing. Before social mixing, testosterone did not modify the frequency of aggressive interactions, while it increased the probability of an animal to receive an aggression. After social mixing testosterone-treated animals initiated and received more aggressions than control animals. Moreover, after social mixing, testosterone-treated animals directed their aggressions mainly towards unfamiliar animals, whereas control animals directed theirs aggressions towards familiar and unfamiliar animals in the proportion expected by chance. It is suggested that the effects of testosterone on aggressive behaviour are context dependent, and that testosterone increases an animal's tendency to establish dominance relationships, rather than its aggressiveness per se.

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[Preliminary pilot study of cyproterone acetate for the treatment of aggressive behavior associated with severe dementia].

INTRODUCTION: Behavioral symptoms are common in dementia, and seem to be more frequent in men than in women. Agitation is frequently responsible for caregiver burn-out and leads to institutionalization. The dramatic increase in the prevalence of Alzheimer's disease and related disorders requires better management of behavior symptoms. Although environmental adaptation has been proposed recently, for many years, psychoactive medications and physical restraints were the primary approach. However, in severely demented patients, both pharmacologic and non-pharmacologic treatments are inoperative. In this situation, alternative pharmacologic approach should be tested. Cyproterone acetate, an antiandrogen and progestative steroid has never been proposed to prevent aggressive behavior in dementia, but its favorable effect is well described in rat and monkey aggressivity. PATIENTS AND METHODS: Cyproterone acetate was proposed for 19 demented patients who developed severe aggressive behaviors or an agitation unresponsive to psychoactive drugs (even in association) or to environmental adaptation. Clinical and behavioral analysis was carried out using the Cohen-Mansfield agitation inventory associated with an assessment of dependency in daily life activities, before and during treatment with cyproterone acetate. The behavioral status was stable, with permanent or repetitive agitation. Seven patients had vascular dementia, 7 had Alzheimer's disease, 2 had fronto-temporal degeneration, 2 had Huntington's disease and 1 a probable diffuse Lewy bodies disease. Fifteen patients had prominent aggressive behavior and 4 had predominant aberrant motor behavior with aggressive behavior. RESULTS: Cyproterone (50 to 100mg - mean: 92.5mg daily) improved significantly aggressive and impulsive behavior related to Alzheimer's disease or vascular dementia but had no effect on aberrant motor behavior. When cyproterone was stopped, aggressive behaviors reappeared more rapidly in vascular dementia. CONCLUSION: Cyproterone acetate is then an interesting choice when aggressive behavior is not improved with psychotropic drugs. A detailed clinical analysis is required to avoid the use of cyproterone in non-aggressive and non-impulsive patients. The results of this preliminary study suggest a randomized double-blind study should be carried out in the near future. The behavior improvement could be related to the blockage of androgen receptors, and simultaneously to the sedative effect of progestative drugs.

Aged↗

Catecholaminergic involvement in the control of aggression: hormones, the peripheral sympathetic, and central noradrenergic systems.

Noradrenaline is involved in many different functions, which all are known to affect behaviour profoundly. In the present review we argue that noradrenaline affects aggression on three different levels: the hormonal level, the sympathetic autonomous nervous system, and the central nervous system (CNS), in different, but functionally synergistic ways. Part of these effects may arise in indirect ways that are by no means specific to aggressive behaviour, however, they are functionally relevant to it. Other effects may affect brain mechanisms specifically involved in aggression. Hormonal catecholamines (adrenaline and noradrenaline) appear to be involved in metabolic preparations for the prospective fight; the sympathetic system ensures appropriate cardiovascular reaction, while the CNS noradrenergic system prepares the animal for the prospective fight. Indirect CNS effects include: the shift of attention towards socially relevant stimuli; the enhancement of olfaction (a major source of information in rodents); the decrease in pain sensitivity; and the enhancement of memory (an aggressive encounter is very relevant for the future of the animal). Concerning more aggression-specific effects one may notice that a slight activation of the central noradrenergic system stimulates aggression, while a strong activation decreases fight readiness. This biphasic effect may allow the animal to engage or to avoid the conflict, depending on the strength of social challenge. A hypothesis is presented regarding the relevance of different adrenoceptors in controlling aggression. It appears that neurons bearing postsynaptic alpha2-adrenoceptors are responsible for the start and maintenance of aggression, while a situation-dependent fine-tuning is realised through neurons equipped with beta-adrenoceptors. The latter phenomenon may be dependent on a noradrenaline-induced corticosterone secretion. It appears that by activating very different mechanisms the systems working with adrenaline and/or noradrenaline prepare the animal in a very complex way to answer the demands imposed by, and to endure the effects caused by, fights. It is a challenge for future research to elucidate how precisely these mechanisms interact to contribute to functionally relevant and adaptive aggressive behaviour.

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Aggressive behavior in inbred strains of mice during pregnancy.

Female aggressive behavior toward adult male ICR/JCl mice was compared for virgin and pregnant mice of five inbred strains (BALB/c, C3H/He, C57BL/6, DBA/2J, and AKR/J). Pregnant females from four strains except BALB exhibited intense aggressive behavior, whereas only virgin AKR females were aggressive. Aggressive behavior began in early pregnancy, was highest in midpregnancy, and declined slightly thereafter until the day of parturition. The level of aggressive behavior showed significant strain differences. The topography of aggressive behavior was also different among the four strains. DBA females showed marked contrast with the other three strains in the temporal changes of aggression in the first phase of encounter. Furthermore, strain specific behavioral pattern of aggression was demonstrated based on six behavioral acts ( Darting , Chasing, Attack, Biting, Wrestling, and Boxing). Virgin and pregnant AKR females showed the identical behavioral pattern of aggression.

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Relationship between central serotonergic function and aggression in prepubertal boys: effect of age and attention-deficit/hyperactivity disorder.

Data indicate that diminished central serotonergic (5-HT) function is related to aggression in adults, but discrepant findings in children suggest that age or the presence of attention-deficit/hyperactivity disorder (ADHD) may influence this relationship. This study examined whether age or ADHD affects the association between 5-HT and aggression in 7-11-year old clinically-referred boys. Forty-six boys were divided into non-aggressive ADHD, aggressive ADHD, and aggressive non-ADHD groups based on responses to interviews and ratings of behavior. Central 5-HT function was assessed by measuring the prolactin response to a 1-mg/kg oral dose of D,L-fenfluramine. There was no significant difference in the prolactin response across the three groups of boys. Furthermore, when examined dimensionally, prolactin response was largely unrelated to ratings of aggression, even after controlling for ADHD. Finally, age was not associated with prolactin response, and had no effect on the relationship between prolactin response and aggression. This study provides further evidence that there is no clear relationship between central 5-HT function and aggression in disruptive boys. Moreover, these data do not confirm the hypothesis that age or the presence of ADHD influence the relationship between 5-HT and childhood aggression.

Age Factors↗

Assessment of life history of aggression: development and psychometric characteristics.

The Life History of Aggression (LHA) assessment was administered to up to 252 subjects. In addition to a total LHA score, subscale scores for Aggression, Social Consequences and Antisocial Behavior, and Self-directed Aggression were calculated. Test-retest stability, interrater agreement, and internal consistency reliability were excellent both for the LHA Total score and the LHA Aggression subscore. There were moderately strong correlations between these scores and both self-reports of aggressive tendency (Buss-Durkee Hostility Inventory: n = 214) and recent overt aggression (Overt Aggression Scale-Modified for Out-patients: n = 61). LHA Total scores were highest among subjects with Antisocial or Borderline Personality Disorder. These results support the use of the LHA assessment, and especially the LHA Aggression subscore, as a measure of life history of aggressive behavior.

Adult↗

The impact of men's alcohol consumption on perpetration of sexual aggression.

Epidemiological and experimental literature examining the link between men's alcohol consumption and perpetration of sexual aggression is reviewed. The following are included in the review: (1) associational studies that examine the correlation between typical alcohol consumption and history of sexual aggression perpetration; (2) event-level studies that examine the impact of alcohol consumption at the time of sexual assault; and (3) experimental studies that consider the impact of administered alcohol on men's responses to a sexual aggression analog. Associational studies suggest a modest correlation between typical alcohol consumption and history of sexual aggression perpetration, but spurious effects may account for much of the relationship. Event-level studies offer mixed evidence in support of a relationship between alcohol consumption at the time of the sexually aggressive incident and severity of outcome. Experimental analog studies provide evidence of a proximal, pharmacological effect of alcohol on the likelihood of sexual aggression perpetration and more modest evidence supporting an alcohol expectancy effect. An integrative heuristic model of alcohol's distal and proximal effects on sexual aggression perpetration is proposed. Priorities for future research include greater specificity in measurement of sexual aggression, examination of alcohol's indirect effects on aggression through context, and consideration of mechanisms other than alcohol myopia in understanding alcohol's proximal effects.

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Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates.

Objective measures of experimentally-induced aggressiveness were evaluated in 20 methadone-treated heroin addicts, in comparison to 20 normal healthy male subjects. All the subjects were submitted to preliminary DSM IV interviews, Buss Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the point subtraction aggression paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money, which was attributed to a fictitious other participants. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response), or protecting their counter (escape response). Money-earning responses were significantly lower (t=4.38, P<0.001) and aggressive responses significantly higher (t=5.45; P<0.001) in methadone patients in comparison to controls. During the experimentally-induced aggressiveness, plasma adrenocorticotropic hormone (ACTH), cortisol (CORT) and growth hormone (GH) concentrations increased significantly less and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), significantly more in methadone subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamines changes, BDHI 'direct' and 'irritability' scores, MMPI 'psychopathic deviate' scores both in methadone subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between methadone doses, or exposure extent, and aggressiveness levels. Our findings suggest that heroin dependent patients have higher outward-directed aggressiveness than healthy subjects, in relationship with monoamines hyper-reactivity, also under methadone medication. Aggressiveness in methadone patients seems to be related more to the personality traits than to drug effects. Hypothalamus-pituitary-adrenal (HPA) axis responses, unexpectedly dissociated from catecholamines rise among methadone patients, could be due to a long-lasting inhibitory action exerted by opiates on pro-opio-melanocortin (POMC), or to a premorbid psychobiological condition that exhausted hormonal reactivity.

Adult↗

Polyunsaturated fatty acid status and aggression in cocaine addicts.

BACKGROUND: There is mounting evidence that low levels of some polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of aggressive disorders. PUFA status is influenced by nutritional factors and because of our observation that some substance abusers have poor dietary habits, we explored the possibility that the fatty acids (FA) profiles of cocaine addicts with and without aggressive tendencies would differ. We also explored the possibility that their FA levels would change after a 2 week stay on an inpatient unit where a standard diet would be provided. METHODS: Plasma levels of FAs were measured in 24 cocaine addicts admitted to an inpatient substance abuse unit. Six patients had a past history of aggression and 18 did not. RESULTS: A comparison of the FA levels of aggressive and non-aggressive patients performed 3.7+/-2.0 days after their admission did not reveal any significant difference in saturated FAs (SFAs) or monounsaturated FAs (MFAs). Aggressive patients had significantly lower levels of the n-6 PUFA docosapentaenoic acid (DPA), of total n-3 PUFAs and of the n-3 PUFA docosahexaenoic acid (DHA), and a marginally significant increase in the ratio of n-6 to n-3 PUFAs. Measurements performed 18.4+/-1.3 days after admission showed that most FAs had increased in the two patient groups. Some PUFAs, especially those of the n-3 series, increased more sharply in the aggressive patients. As a result, PUFA differences between groups that were present shortly after admission became non-significant. CONCLUSIONS: These data suggest that patients' diets prior to their hospitalization were less than optimal and that the diet of the aggressive individuals might have been particularly deficient in n-3 rich nutrients. These data also give additional support to evidence indicating a possible link between an n-3 deficiency and aggression in humans.

Adult↗

Aggression escalated by social instigation or by discontinuation of reinforcement ("frustration") in mice: inhibition by anpirtoline: a 5-HT1B receptor agonist.

Experiments with social instigation or the omission of scheduled reinforcement show that serotonergic mechanisms may be involved in escalated aggression in animals. 5-HT1B receptor agonists have anti-aggressive effects in individuals who show moderate as well as high levels of aggression. The present study compared the effects of the 5-HT1B agonist anpirtoline (0.125-1.5 mg/kg) on (1) species-typical aggressive behavior in male mice, (2) aggression "instigated" or primed by prior exposure to the opponent, and (3) aggression heightened by "frustration" caused by omission of scheduled reinforcement. The effects of anpirtoline on species-typical behavior were also assessed after pretreatment with the 5-HT1B/1D receptor antagonist GR127935 (10 mg/kg). Anpirtoline, like other 5-HT1B agonists (CP-94,253, zolmitriptan), decreased both instigated and frustration-heightened aggression, while motor behavior was unaffected. The aggression-inhibiting effects of anpirtoline were blocked by pretreatment with GR127935. The current results indicate that the 5-HT(1B) receptor is critically involved in the modulation of escalated aggression.

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Stability of interindividual differences in serotonin function and its relationship to severe aggression and competent social behavior in rhesus macaque females.

Few studies have investigated longitudinally interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations in adult nonhuman primates across time and between baseline and stressful conditions. Furthermore, whereas studies with male macaques consistently have reported a significant, negative correlation between CSF 5-HIAA and rates of spontaneous aggression, wounding, and severe aggression, very few studies have examined this relationship in adult female nonhuman primates. Even fewer studies have investigated correlations between CSF 5-HIAA and competent social behavior, such as social dominance, in female monkeys. In the present study, two social groups of adult rhesus monkeys (Macaca mulatta) were formed by placing 16 females (aged 42 to 180 months, mean age: 68 months) in one of two indoor-outdoor enclosures with one or two adult males. CSF norepinephrine (NE), monoamine metabolites, and behavioral data were collected systematically over a 24-week period. In week 5 of the study, one additional female, not familiar to any of the other subjects, was added to each social group. Thereafter the groups were left undisturbed, and data characterizing spontaneous aggressive wounding and severe wound injuries in the females were collected for an additional year. The results showed that both group introduction and the addition of a new subject into each group resulted in increased monoamine turnover in the animals within the social groups. Interindividual differences in CSF concentrations of each of the monoamine metabolites and NE were highly stable from the baseline period to the stress samplings, and between stress samplings. Females with low CSF 5-HIAA exhibited higher rates of spontaneous aggressive wounding, and they were more likely to be removed from their social groups for aggressive wounding and/or treatment of injuries. CSF NE concentrations also were negatively correlated with rates of spontaneous aggression. In contrast, competitive aggression, i.e. noninjurious aggression used to maintain social dominance ranking, was not correlated with CSF 5-HIAA or NE. Females with above average CSF 5-HIAA prior to and following group formation were more likely to attain and maintain a high social dominance ranking within their social group than females with below average CSF 5-HIAA. The present findings indicate that CNS monoamine functioning in adult female rhesus macaques is traitlike, showing a high degree of interindividual stability across time and setting. These findings also suggest a role for serotonin in controlling impulses that regulate aggression and that competent social behavior among nonhuman primates may require average or above average serotonin functioning.

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Aggressive behaviour and platelet 3H-paroxetine binding in schizophrenia.

Forty schizophrenic patients were included in a study of the relationship between serotonin function as measured by 3H-paroxetine binding to platelet membranes and aggressive behaviour. Patients classified as either aggressive or non-aggressive were paired by age, sex and duration of illness. 3H-Paroxetine binding variations were avoided by taking samples for each pair between 09:00 and 11:00 h, within 4 days of each other, and by assaying pair of samples together. The mean Kd for the aggressive group was 0.193 +/- 0.126 nM and the mean Kd for the non-aggressive group was 0.176 +/- 0.164 nM. The mean Bmax for the aggressive group was 1451 +/- 386 fmol/mg protein while the mean for the non-aggressive group was 1549 +/- 375 fmol/mg protein. There was no significant difference between the groups for either parameter, Kd or Bmax. There were no significant correlations between psychopathology rating including positive and negative symptoms, depression, suicidal thoughts, impulse control, as well as both past and present history of aggression, hostility and irritability traits, psychopathic deviance and either Bmax and Kd. This study finds no relationship between aggressive behaviour and peripheral serotonin function as measured by 3H-paroxetine binding to platelet membranes.

Adult↗

Norepinephrine function in personality disorder: plasma free MHPG correlates inversely with life history of aggression.

OBJECTIVE: Clinical and pre-clinical data suggest the possibility of a facilitory role for norepinephrine (NE) in impulsive-aggressive behavior. While clinical studies have focused on putative central measures of NE activity, few studies have been published using peripheral measures. In this study, the relationship between plasma free NE metabolite, plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG), and impulsive aggression was explored in subjects with personality disorder. METHODS: Subjects were 30 male subjects with personality disorder in whom basal plasma free MHPG concentrations were obtained. Aggression was assessed using the Life History of Aggression (LHA) assessment and the Buss-Durkee Aggression scales; impulsivity was assessed using the Barratt Impulsiveness and the Eysenck Personality Questionnaire Impulsivity scales. RESULTS: A significant inverse correlation was found between LHA-Aggression and pMHPG in these subjects. Correlations with other behavioral measures were not statistically significant. pMHPG was significantly lower among subjects with borderline personality disorder but not significantly lower after controlling for LHA-Aggression scores. CONCLUSION: These data suggest that pMHPG is inversely correlated with life history of aggression in subjects with personality disorder and that central and/or peripheral NE may play a role in modulating aggressive behavior in these subjects.

Adult↗

Perception of aggression among psychiatric nurses in Switzerland.

OBJECTIVE: To identify principal components and patterns in the perception of aggression by psychiatric nurses and to explore relationships between the perception of aggression and personal and workplace characteristics. METHOD: Seven hundred and twenty-nine nurses working in psychiatric inpatient departments of German-speaking Switzerland completed the perception of aggression scale (POAS). Data analysis included factor analysis, group comparisons and multivariate analysis of covariance. RESULTS: Two plausible factors were identified, representing different dimensions in the perception of aggression and accounting for 35% of the variance. Firstly, aggression is perceived as dysfunctional/ undesirable and, secondly, aggression is perceived as a functional/ comprehensible phenomenon. Only minor differences were found in the perception of aggression with regard to personal characteristics or work environment of the nurses. CONCLUSION: Nurses perceive aggression not just as a negative phenomenon. The perception of aggression as measured by POAS is independent of many characteristics expected to be related to the perception of violence, such as grade of education, work experience, etc.

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Facilitating effects of erotica on aggression against women.

In order to examine the effects of highly erotic stimuli on aggression against females, male subjects were angered by a male or female confederate and exposed to an erotic film, an aggressive film, or a nonfilm condition. Subjects were given two opportunities to aggress against the confederate. It was found that both the aggressive and the erotic films increased aggression against both targets during the first and second aggression opportunities. However, the erotic film facilitated aggression against the female target across the two aggression sessions. The processes operating to cause this increase are discussed in terms of reducing restraints against aggressive behavior and the specific cue value of erotic films.

Aggression↗