Aggression In Male Mice Research Articles

Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny

Testosterone (T) and estradiol (E 2) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behavior via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E 2, by the enzyme aromatase. Both the levels of brain aromatase activity (AA) and the effects of T and E 2 on aggressive behavior in adulthood depend on steroidal organization of the CNS during ontogeny. In this study we measured plasma T and in vitro brain AA of male fetuses and neonates derived from two strains of wild house mice, which had been genetically selected for aggression, based upon attack latency. There were no differences in preoptic area (POA) AA levels between selection lines on either embryonic day (E) 17 or 18, or the day after birth (day 1). In the non-aggressive long attack latency (LAL) males the POA AA increases with age, i.e. was higher on E18 than on E17, which is correlated with brain weight (BrW). This was in contrast to aggressive short attack latency (SAL) fetuses, which only showed a slight, but not significant difference between embryonic days or a correlation with BrW. Neonatally, the POA AA of LAL males tended to decrease in contrast to SAL males. However, SAL neonates had a higher AA in the amygdala (Am) than LAL neonates, whereas no differences exist in the anterior hypothalamus. Thus, a differential brain AA distribution exists in SAL and LAL pups. At day 1 SAL males show higher AA in the Am than in the hypothalamus (POA + AH), whereas in the LAL strain the AA did not differ between these brain areas. In the LAL males plasma T levels decreased from E17 to day 1, whereas the SAL neonates (day 1) exhibited higher circulating T concentrations than LAL neonates. These results suggest a T-independent aromatase induction prenatally in both selection lines, whereas neonatally the higher plasma T level in the SAL line coincides with higher AA levels in the Am. Accordingly, a differential pattern of E 2 formation exists in the brains of the two selection lines during ontogeny. The variation in circulating T and maximal brain E 2 formation around birth might result in a differential organization of adult CNS sensitivity to sex steroids and accordingly differences in aggressive behavior.

Acute and chronic effects of clomipramine on isolation-induced aggression in male mice

The behavioral effects of clomipramine were studied on an ethopharmacological model of aggression. A range of low doses (similar to those used in clinical practice: 1.5, 3, and 6 mg/kg) and a higher dose (24 mg/kg—more usual in animal experimentation) were administered to isolated male mice that confronted anosmic opponents in a neutral arena. Encounters were staged 30 min after acute treatment and either 30 min or 24 h after the last drug administration in the chronic (21-day) treatment. Significant behavioral effects were observed predominantly with the highest dose. Acute and chronic effects were similar in the sense that both decreased aggressive behavior and produced some impairment of motor behavior, but differed in that such antiaggressive action was more potent in the chronic treatment, whereas the motility impairment was stronger in the acute one. The two chronic evaluations (at 30 min or 24 h) did not produce widely different results.

The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice.

The role of serotonergic (5-HT) receptor subtypes in mediation of aggressive behaviour in isolated male mice has been studied. Increase of attack latency was used as a simple measure of antiaggressive behaviour. 5-HT1A agonists (BAY R 1531, 8-OHDPAT, flesinoxan, gepirone, 5MeO DMT, buspirone, ipsapirone, BMY 14802) completely inhibit the aggressive behaviour irrespective of their intrinsic activities. Also the putative antagonists spiroxatrine and NAN 190 as well as the non-selective 5-HT1 agonists RU 24969, TFMPP, mCPP and eltoprazine have an antiaggressive effect. The mixed 5-HT1A and beta-adrenoceptor antagonists (-)-alprenolol and pindolol are ineffective and do not inhibit the effect of 8-OHDPAT. Neither does the non-selective 5-HT antagonist metergoline. The antiaggressive effect correlates with 5-HT1A receptor affinity in vitro and with generalization to the 8-OHDPAT-induced discriminative stimulus. The selective 5-HT uptake inhibitor citalopram does not inhibit aggressive behaviour. The 5-HT2 agonist DOI has an antiaggressive effect only at high doses, whereas the 5-HT2 antagonist ritanserin and the 5-HT3 antagonist ondansetron are ineffective. Prazosin (alpha 1-adrenoceptor antagonist), clonidine (alpha 2-adrenoceptor agonist), clenbuterol (beta-adrenoceptor agonist), ketanserin (5-HT2 receptor and alpha 1-adrenoceptor antagonist), clozapine and (-)-octoclothepin (dopamine (DA), 5-HT2 receptor and alpha 1-adrenoceptor antagonist) all show an antiaggressive effect. SCH 23390 (DA D1 receptor antagonist) and emonapride (DA D2 receptor antagonist) are ineffective. In conclusion, 5-HT1A receptors are involved in mediation of isolation-induced aggressive behaviour in mice. The involvement of other 5-HT receptor subtypes needs further clarification. The adrenergic system may also be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethological analysis of the effects of MK-801 upon aggressive male mice: Similarity to chlordiazepoxide

Previous studies have demonstrated benzodiazepine-like effects of competitive and noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) type of excitatory amino acid receptor. The present experiment compared the effects of the benzodiazepine chlordiazepoxide and the NMDA noncompetitive antagonist MK-801 upon the behavior of aggressive male mice in dyadic interactions using ethological analysis. OF-1 male mice housed with females were administered either chlordiazepoxide (Vehicle, 3.0, 10.0 and 30.0 mg/kg IP) or MK-801 (Vehicle, 0.1, 0.3 and 0.3 mg/kg, IP) in a randomised order thirty minutes prior to pairing with unfamiliar male opponents in an unfamiliar environment. It was found that both compounds tended to increase aggressiveness and social behavior and reduce ambivalent activity consistent with approach-avoidance conflict. The increases in aggressiveness and decreases in ambivalent activity were induced by MK-801 at doses lower than those resulting in gross motor effects. These data confirm that competitive antagonists of NMDA may generate a benzodiazepine-like behavioral profile.

Behavioural strategies of aggressive and non-aggressive male mice in response to inescapable shock

The effect of exposure to inescapable long-duration shocks of moderate intensity on intershock activity and on subsequent escape or avoidance performance was studied in aggressive and non-aggressive male mice. The activity of the non-aggressive mice was severely suppressed during the inescapable shock session, while that of the aggressive males was hardly influenced. The decremental effect of prior shock exposure on subsequent response latency and activity in an active two-way escape or avoidance task was greater in the non-aggressive than in the aggressive mice. There was no evidence that learned inactivity or learned helplessness (an associative deficit) could explain the results. Instead, individual differences in behavioural strategy in response to threatening situations appeared to account for the effects of inescapable shock. Aggressive male mice predominantly adopted an active behavioural strategy in challenging situations, which resulted in persistent attempts to exercise control over the external situation and hence in a sustained tendency to initiate responses. Non-aggressive mice primarily assumed a passive strategy; their tendency to exercise control was low, which readily resulted in a reduced tendency to initiate responses.

Effect of type of opponent on aggression in male mice with particular reference to studies with antihormones

The potential influence of the type of opponent used in intermale aggression encounters to assess the actions of drugs was examined. Two experiments were carried out, one with the antiandrogen Cyproterone Acetate and the other with the antioestrogen CI-680 (both administered every three days over 25 days). In both experiments the antihormone-treated subjects encountered different opponents, namely: a) an antihormone-treated male, b) a non aggressive anosmic male or c) a vehicle-treated male. Vehicle-treated subjects also confronted a vehicle-treated or an anosmic opponent. The behaviour displayed by antihormone-treated subjects varied according to the characteristics of the partner, suggesting that the effects of drugs might be interpreted differently depending on the type of animal employed as an adversary. In fact, some of the apparently contradictory results reported in the literature seem to be consequences of the utilisation of different kinds of opponents. It is concluded that the choice of the opponent is of paramount importance in the study of drug actions on intermale aggression tests and that using more than one type of opponent can provide more complete information about the actions of particular drugs.

Aggression in male mice: Rapid-onset attack of lactating female mice following termination of hyperphysiological testosterone treatment

Gonadally-intact or castrated and testosterone-(T) treated male mice display aggressive behavior towards olfactory-bulbectomized male (OBM) stimuli, but not towards lactating female (LF) stimuli. By comparison, T-treated female mice display aggressive behavior towards both OBM and LF stimuli. The purpose of the present experiment was to determine if male mice given hyperphysiological T-treatment would display “female-typical” attack of OBM and LF stimuli. Hyperphysiological T-stimulation did not lead to the display of aggressive behavior towards OBM and LF stimuli; only OBM stimuli were attacked, suggesting a qualitative behavioral sex difference in response to T. However, the major finding of this study occurred following the termination of T-treatment. Castrated males that had previously received hyperphysiological T-treatment began to attack LF stimuli within 48 hr of treatment termination. By comparison, castrated males that had previously received physiological T-stimulation, as well as a gonadally-intact control group, generally began to attack LF stimuli 3–4 weeks following treatment-termination/castration. It is suggested that this unusual treatment-termination-induced behavioral display occurs via neurochemical mediation.

Effects of classical and atypical antipsychotic drugs on isolation-induced aggression in male mice

A series of classical, atypical and putative antipsychotic drugs were compared for their ability to inhibit isolation-induced intraspecies aggression with affinity for D-2 dopamine receptors and induction of akinesia. The majority of drugs tested significantly inhibited aggressive behavior only after doses that greatly decreased the ability of mice to move. Even though akinesia seemed to account for inhibition of aggression there was no apparent correlation with binding to striatal D-2 receptors.

Changes in male odours and urinary marking patterns due to inhibition of aggression in male mice

The effects of active inhibition of aggression on male odours and urinary marking patterns were studied in mice belonging to a highly aggressive strain the TA (Turku Aggressive), which has been developed by selective breeding through 37 generations. These males were defeated by trained fighters until they showed no aggression. Individually housed TA males served as controls. Mice from the parental or Normal Strain, which is intermediate in aggression, were exposed to the odours. The males from the Normal Strain were tested for aggression against male castrates to which urine from the two types of TA males or water had been applied. The urine from the highly aggressive control TA males evoked most aggression. The Normal males were later tested against castrates on soiled sawdust. Fewer attacks occured on sawdust soiled by the urine from the control TA males. The preferences for areas covered with soiled sawdust were also assessed. The males from the Normal Strain preferred areas soiled by the TA males trained to nonaggressiveness while the females preferred areas soiled by the highly aggressive control TA males. Subsequently the size and number of urinary marks deposited were examined. The TA males trained to nonaggressiveness voided urine in fewer but larger pools. The differences showed the same direction as those previously found between the TA and TNA strains, selectively bred for aggression and non-aggression, respectively. In mice the odour signals and urinary marking patterns seem to be correlated with the level of aggressiveness, either hereditarily determined or acquired through learning.

Inhibition of the enzymatic reaction of renin in aggressive mice.

Aggressive behaviour provokes a very high increase in plasma renin in aggressive male mice. We demonstrate that this occurs in mice with high as well as low concentrations of renin in the submaxillary glands, although the highest values were seen in the former. Plasma renin and angiotensinogen concentrations, as well as plasma renin activity, were measured before and after aggression. The theoretical plasma renin activity (generation rate of angiotensin l) was calculated from kinetic parameters and the renin and angiotensinogen concentrations. The Km (Michaelis constant) was 3 mumol/l and the kcat (turnover number) was 0.15/s for the reaction between pure submaxillary mouse renin and mouse angiotensinogen. The measured plasma renin activity was much lower than that calculated from both the kinetics and the fall in angiotensinogen concentration. The decrease in angiotensinogen in vivo was independent of the renin concentration. Intraperitoneally injected renin mimicked the aggression-provoked renin increase and resulted in better agreement between measured and calculated parameters. This indicates, that during aggression, the mouse can inhibit and control the renin-angiotensinogen reaction.

Lead, age and aggression in male mice

The impact of eleven weeks of ingestion of a 0.5% lead acetate solution on agonistic behavior of male Binghamton Heterogeneous stock mice (either 120 or 660 days of age) was examined. Similar aged mice were paired for aggression testing. Not surprisingly, younger mice, regardless of fluid history fought more vigorously than older mice. However, when mice of similar fluid history were paired together, lead ingestion decreased the latency to fight only in older mice. Regardless of their prior fighting history, when lead treated mice fought similar aged controls, the lead exposed mice in younger pairs were typically subordinate; but in older pairs, lead exposed mice were dominant. These results, coupled with extant literature concerning age-related changes in endocrine function, pituitary-adrenal activity, and lead-induced changes in hippocampal function suggest that future work directed at mechanism(s) underlying lead-induced alterations in agonistic behavior should consider life span changes in biobehavioral profiles.

A guide to the literature on aggressive behavior

A guide to the literature on aggressive behavior

Stimulation of aggression in male mice by α-MSH and its relation to light phase and to saline intake effects

The resident/intruder test was used to examine the social approach and aggressive behaviour of male albino mice. Digging, self-grooming and rearing were also recorded, as was the post-test response to hot-plate exposure. The resident mice were given either a single acute injection of MSH (MSH); 0.9% NaCl to drink (for 48 h prior to testing; SAL); a combination of both treatments (MSH + SAL) or an injection of 0.9% physiological saline (control group; CON). Testing was carried out at the midpoints of the light and dark phases of the 12:12 light cycle. Data on plasma ion levels and hypothalamic cAMP levels were collected after the hot-plate test. MSH stimulated fighting both in the light and dark, and SAL in the light. MSH + SAL reversed the effects of the single treatments in that fighting declined below CON levels in both light and dark. Social contact and other behaviours were much less affected by treatments. Pain responding and plasma ion levels were not changed. Effects on cAMP were largely inconclusive, but intruders had significantly lower levels than the aggressive resident animals.

Testosterone modulates the effects of ethanol on male mouse aggression.

In a series of three experiments, we evaluated the degree to which the effects of acutely administered ethanol on aggressive behavior of male CFW mice toward a male intruder interact with, and depend on, androgen levels. In the first experiment, mice were tested at 15 min after 0, 0.1, 0.3, 1.0, 1.7, or 3.0 g/kg of ethanol PO. The highest dose (3.0 g/kg) significantly suppressed aggression by the male residents. In the second experiment, aggressive behavior was suppressed from 5 to 60 min after 3.0 g/kg ethanol administration PO. The third experiment evaluated the role of testosterone in these effects in another set of male mice that were castrated and then implanted with a 7.5-mm or 2.5-mm silastic capsule of testosterone (T) or a silastic capsule containing cholesterol as a control. The castrated mice with 2.5-mm T capsules or cholesterol capsules had lower baseline levels of aggression than intact mice or castrated males with 7.5-mm T capsules, but they demonstrated an alcohol dose-response pattern similar to that of the intact males. The castrated males with 7.5-mm T capsules had a different dose-response curve than the other males. Doses of 1.0 and 1.7 g/kg ethanol PO significantly enhanced aggression; 5.6 g/kg was required to suppress aggression. Ethanol effects on aggressive behavior did not require T or changes in T level, but T levels altered behavioral sensitivity to ethanol.

Increase in aggressiveness of male mice carrying a reciprocal translocation, T(10,13), in the heterozygous state

The agonistic behavior of inexperienced pairs of agouti male mice was determined by counting the bites received from and delivered to the opponent within 24 h. The first 10 min of agonistic encounters was recorded by videotape to analyze the frequency and duration of 10 behavioral traits. Each pair consisted of two F1 males from the cross of (101/C3H)♂ x NMRI♀, one of which (test male) was derived from a father carrying a reciprocal translocation, T(10,13), in the heterozygous state, while the other (standard opponent) stemmed from a chromosomally normal father of the same origin. Since the offspring of a heterozygous translocation are segregating into chromosomally normal and translocation mice, the test male was either chromosomally normal or a carrier of the translocation in the heterozygous state. Apart from the translocation, all males were of the same genotypic constitution. Comparing the differences between translocation carriers and chromosomally normal mice relative to their standard opponent, significantly more winners than losers were found among the translocation carriers. The differences of 10 behavioral traits between the test male and his opponent revealed significantly more contacts, pursuits, and attacks and significantly fewer defense and flight responses of the test males when this was a carrier of the heterozygous translocation, T(10,13).

Sexual behavior and aggression in male mice: involvement of the vomeronasal system

Recent observations have implicated the vomeronasal (accessory olfactory) system in the chemosensory control of rodent social behaviors. The purpose of this study was to observe the effects of peripheral vomeronasal organ extirpation on sexual behavior, aggression, and urine marking in male mice. Relative to sham-operated control animals, mice lacking vomeronasal organs displayed significantly reduced levels of copulatory behavior and intermale aggression. Urine marking rates were not reduced. The peripheral removal of the vomeronasal organ resulted in complete bilateral deafferentation of the accessory olfactory bulbs but spared the peripheral input to the main olfactory bulbs as evidenced by the lack of anterograde vomeronasal nerve transport but normal anterograde olfactory nerve transport of intranasally applied horseradish peroxidase. Neither body weights, paired testes weights, nor seminal vesicle weights of mice with vomeronasal system lesions differed significantly from those of control animals. Thus, an intact vomeronasal organ is important for the normal display of sexual behavior and aggression in male mice, and the reductions in these androgen-dependent behaviors following peripheral deafferentation of the vomeronasal system cannot be attributed to a chronic reduction of gonadal hormone secretion.

High Fetal Estrogen Concentrations: Correlation with Increased Adult Sexual Activity and Decreased Aggression in Male Mice

In the house mouse (Mus musculus), fetuses may develop in utero next to siblings of the same or opposite sex. The amniotic fluid of the female fetuses contains higher concentrations of estradiol than that of male fetuses. Male fetuses that developed in utero between female fetuses had higher concentrations of estradiol in their amniotic fluid than males that were located between other male fetuses during intrauterine development. They were also more sexually active as adults, less aggressive, and had smaller seminal vesicles than males that had developed between other male fetuses in utero. These findings raise the possibility that during fetal life circulating estrogens may interact with circulating androgens both in regulating the development of sex differences between males and females and in producing variation in phenotype among males and among females.

Social and Historical Foundations of Modern Medicine

Back to table of contents Previous article Next article ArticleNo AccessSocial and Historical Foundations of Modern MedicineEDWARD M. BROWNEDWARD M. BROWNSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.139.6.833-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Social and Historical Foundations of Modern Medicine." American Journal of Psychiatry, 139(6), pp. 833-a–834 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited ByJournal of Neural Transmission, Vol. 123, No. 8The Late Psychosocial Complications in Patients with Posterior Fossa Tumor (Medulloblastoma)Psychiatric Annals, Vol. 43, No. 7International Journal of Primatology, Vol. 34, No. 4Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology, Vol. 23, No. 1Journal of Neural Transmission, Vol. 117, No. 2Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase16 January 2001 | Proceedings of the National Academy of Sciences, Vol. 98, No. 3Annals of the New York Academy of Sciences, Vol. 836, No. 1 NeurobiologyAggressive behavior in institutionalized elders: A theoretical framework4 September 2016 | American Journal of Alzheimer's Disease, Vol. 10, No. 2 Volume 139Issue 6 June 1982Pages 833-a-834 Metrics PDF download History Published online 1 April 2006 Published in print 1 June 1982

The decline of aggressiveness in male mice during group caging as determined by punishment delivered by the cage mates

Group-housed rodents are generally less aggressive than isolated counterparts. The present study examined the role of defeat by cage mates as a reason for this decline in aggressiveness. In Experiment I, highly aggressive isolated male mice were introduced into aggressive or nonaggressive resident groups. The intruder's level of aggressiveness directed toward a group-housed standard opponent declined more rapidly after daily exposure to the aggressive than to the nonaggressive groups. Intruders in the aggressive groups received more attacks from their cage mates, and delivered fewer attacks to them than did the intruders in the nonaggressive groups. In Experiment II, the intruders lived for seven days in small wire net cages in the middle of the group cages. Their level of aggressiveness toward standard opponents decreased little during the preexposure but after being put freely into the groups, their aggressiveness declined to a minimal level within a day. Experiment III showed that when the wire net protection in the middle of the cage was installed after the group caging experience, the aggressiveness of the intruders did not return to the isolation level as effectively as it did in isolation. This is explained by the aggression-inhibiting content that the cues from the cage mates have acquired during group caging. The decline of aggressiveness in male mice during group caging is determined by punishment delivered by the cage mates.

Role of brain dopaminergic mechanisms in rodent aggressive behavior: influence of (+/-)N-n-propyl-norapomorphine on three experimental models.

(+/-)N-n-Propyl-norapomorphine (NPA), a potent agonist of brain dopamine receptors, influences aggressive behavior, but the type of influence depends on the experimental conditions. In rats, NPA increases aggression elicited by electrical foot shock, but decreases predatory aggression against turtles as well as isolation-induced aggression in male mice. NPA proves more potent than apomorphine in both the foot shock and predatory test. A per se ineffective dose of haloperidol (0.05 mg/kg-1 IP) antagonizes NPA in the rat foot shock test as well as in the isolated male mouse test. The relevance of stereotyped movements for NPA influence on aggressive behavior is briefly discussed.