Brain polyamines and aggressive behavior of isolated mice

Brain polyamine levels of male Swiss albino mice which had developed aggressive behavior during isolation, did not differ significantly from those of isolated animals which had not developed aggressivity during isolation, or from those of control animals which were housed in groups. Thus we were unable to confirm the results of Tadano (Folia Pharmac. Jap.70, 457–464, 1974) and Tadano et al. (Folia Pharmac. Jap.70, 9–18, 1974) who had reported that mice made aggressive showed an increase of brain spermidine concentration, which paralleled aggressivity, and which returned to normal values when the aggressive behavior was reversed by grouped housing.     

Motor and neurochemical correlates of aggressive behavior in male mice

We tested aggressive behavior in male albino mice by placing two individuals in one cage. Three successive tests with one-day-long intervals were performed; pairs were formed in a randomized order. Three animal groups, I-III, were classified according to the test results. These were absolute dominants, an intermediate group (animals were sometimes winners in conflicts, sometimes were defeated, or demonstrated no aggressive behavior), and submissive individuals (defeated in all cases). One day before testing and 1 h after each test, the intensity of motor activity (duration and velocity of running in a locomotion wheel ) was measured in all animals. Three days after testing, we measured the levels of noradrenaline (NA)and serotonin (ST) in the hypothalamus and those of NA and adrenaline (A) in the blood. Mice of groups I and II demonstrated high background indices of locomotor activity, while in group III these indices were comparatively low. In the course of testing, these indices in group I were in general preserved, while in groups II and III they dropped significantly. In mice of group I, the highest levels of NA in the hypothalamus and blood, high NA/ST ratio in the hypothalamus, and high NA/A ratio in the blood were observed. Animals of group II were characterized by intermediate levels of NA and ST in the hypothalamus together with rather high concentrations of A and the lowest NA/A ratio in the blood. In mice of group III, the highest level of ST and the lowest NA/ST ratio in the hypothalamus, as well as an intermediate NA/A ratio in the blood, were observed. We conclude that, generally, the response of an animal to emotional stress related to an antagonistic conflict can be classified into three types. These are an NA-ergic type in dominants, an intermediate A-ergic type, and an ST-ergic (vagotonic) type in submissive individuals. These types correlate with the three ethological models of behavior, struggle, escape, and catatonia.Neirofiziologiya/Neurophysiology, Vol. 36, No. 4, pp. 297–305, July–August, 2004.This revised version was published online in April 2005 with a corrected cover date.     

Activation and inhibition of isolation induced inter-male fighting behavior in castrate male CD-1 mice treated with steroidal hormones

Intermale fighting behavior between castrate male CD-1 mice living in isolation and castrate male CD-1 mice living in groups of 10 was activated by treating the isolated males with either testosterone or testosterone propionate. Fighting behavior was not activated by treating isolated males with androstenedione or dihydrotesterone even though these androgens were active in maintaining seminal vesicle weight at levels equal to, or greater than, those observed in gonadally intact males. Neither fighting behavior nor seminal vesicle weight was stimulated by treatment with progesterone, estradiol benzoate, or estradiol benzoate plus progesterone. Concurrent administration of progesterone inhibited fighting behavior activated by low, but not moderate to high doses of testosterone propionate. These results suggest that the hormone requirements for activation of fighting behavior in the male CD-1 mouse are more restrictive than those for maintenance of peripheral target tissues and that progesterone acts in the brain to competitively inhibit androgen-activated fighting.     

Behavioral correlates of aggressive motivation in male mice

The behaviour was studied of male mice of CBA/Lac and C57BL/6j lines near transparent perforated partition in reaction to syngeneic partner which was in adjacent department of the common cage. The number of approaches to the partition and total time of staying near it during testing were used as behaviour parameters. Then the partition was removed and the success or defeat of each individual in agonistic collision and parameters of aggressive reaction of the winner male mouse were fixed. It turned out that future winners spent significantly more time near the partition than future losers. By the correlative analysis reliable interconnections were established between individuals activity near the partition (number of approaches or total time of staying) and intensity of aggression (number or total time of attacks) which reflects the level of the aggressive motivation. Variation is observed of individual correlating parameters depending on animals genotype and conditions of their keeping.     

The development of aggressive and marking behavior in intact and castrated male hamsters.

In pairs consisting of two intact or two castrated male hamsters, the level of aggressive and flank-marking behavior increased with age. Dominance relationships were established early and remained stable. Castration prevented the appearance of the flank gland but did not alter the development of aggression, dominance, and marking. After the formation of intact-castrate pairs, the level of performance of the intacts was significantly higher than the castrates only for marking behavior. In a second experiment involving 49 intact-castrate pairs, there were no differences between intacts and castrates for any behavioral variables measured. Although testicular integrity may influence agonistic behavior in certain situations, these data indicate that it must be only one of several influences in determining the occurrence and outcome of an agonistic encounter.     

The effect of the antiestrogen CI-628 on androgen-induced aggressive behavior in castrated male mice

This study was conducted to determine whether or not the antiestrogen CI-628 would block testosterone-maintained fighting in castrated male mice. TO strain adult male mice were castrated and injected s.c. every day for 14 days with either (1) 75 μg testosterone or (2) 75 μg testosterone and 1 mg CI-628, and in addition 1 mg of CI-628 6 hr prior to each injection of antiestrogen and androgen. Vehicle-injected, castrated, and CI-628-injected animals were employed as controls. Testosterone-maintained intermale aggressive behavior was blocked by the antiestrogen CI-628. This study provides support for the hypothesis that testosterone exerts its effects on the central nervous elements involved in the control of aggressive behavior by its aromatization to estrogenic metabolites.     

Prenatal exposure to androgen influences morphology and aggressive behavior of male and female mice

To assess the effects of prenatal exposure to androgen on adult aggressiveness in mice, pregnant mice were given injections of 1.5 mg testosterone propionate (TP) or oil from Days 12 to 16 of pregnancy. All offspring were gonadectomized on the day of birth. Neonatal treatment occurred on the day following birth and consisted of one-half of the animals from each prenatal treatment group being injected with 100 μg TP while the other half were injected with oil, yielding four Prenatal/Neonatal treatment groups for each sex. On postnatal Day 60, all offspring were given subcutaneous implants of encapsulated testosterone (T) and tested for 10 min every other day against a male opponent until aggression was observed. Female offspring of TP-treated mothers were indistinguishable from males on external examination at birth. The duration of exposure to T required to induce aggression provides an index of the sensitivity of the neural substrate to T. When arranged from the most sensitive to the least sensitive to the aggression inducing action of T, the four Prenatal/Neonatal treatment groups of females were significantly different from each other: Group TP/TP > Group OIL/TP > Group TP/OIL > Group OIL/OIL. A similar pattern was observed for the male offspring. There were no differences in the proportion of animals per group that exhibited aggression (virtually all animals fought) or the intensity of aggression once exhibited. The results demonstrate that morphological and behavioral masculinization can occur in response to exposure to androgen during prenatal as well as neonatal life in mice.     

Involvement of kappa-opioid receptors in mechanisms of aggressive and submissive types of behavior in male mice

Effects of the kappa-opioid receptor agonist U-50.488H (0.0, 0.6, 1.25, 2.5 mg/kg. s.c., 30 min) on behavior of the winner with repeated experience of victories and the losers with repeated experience of social defeat in 20 daily agonistic confrontations as well as the control mice were investigated in the tests estimating exploratory activity (open-field) and communication (partition test). Different effects of drug on behaviors of animals with different social story were shown in both tests. In the losers, all doses of U-50.488H had anxiolytic effect, increasing the communication in the partition test. In the winners, the drug induced an increase of aggressive motivation. The control mice were less sensitive to the treatment. In the open-field test, U-50.488H increased the locomotor and exploratory activity in high anxious losers. Winners significantly differed in their reaction to drug treatment in most behavioral forms in comparison with the controls and losers. It was concluded that kappa-opioid receptors are specifically involved into mechanisms of formation of aggressive or submissive types of behaviors under positive or negative social experience.     

Liver injury after an aggressive encounter in male mice

Acute and intense psychological stressors induce cell damage in several organs, including the heart and the liver. Much less is known about social stress. In male mice, aggressive behavior is the most common social stressor. It is remarkable that upon fighting, submandibular salivary glands release a number of peptides into the bloodstream including epidermal growth factor (EGF). We showed previously that released EGF protects the heart from cell damage in this particular stressful situation. Here, we studied the effect of an aggressive encounter on the liver and whether EGF has a similar effect on this organ. An aggressive encounter in male mice caused inflammatory response and a transient increase in plasma alanine and aspartate transaminase activities. At 3 h, focal infiltration of neutrophils was observed in liver parenchyma. These cells accumulate on eosinophilic hepatocytes, which may correspond to dying cells. A few hours later, evidence of necrotic lesion was observed. Surgical excision of submandibular glands, sialoadenectomy, did not prevent the rise in plasma EGF concentration and did not affect the increase in plasma transaminase activities. Neither did the administration of tyrphostin AG-1478 (inhibitor of EGF receptor kinase) alter the increase in plasma alanine transaminase activity. However, it did enhance the rise in both aspartate transaminase and creatine kinase activity, suggesting heart damage. We conclude that an aggressive encounter causes mild liver damage and that released EGF does not protect this organ, in contrast to its effect on the heart.     

Effects of repeated experience of aggression on aggressive motivation and development of anxiety in male mice

The sensory contact technique allows an aggressive type of behavior to be formed as a result of repeated experience of social victories in daily agonistic confrontations. In mice of the low-aggressive and high-emotional CBA/Lac strain repeated positive fighting experience increases plus-maze anxiety. Behavioral reactivity of males to other conspecifics in the partition test (which measures aggressive motivation) significantly rises. It is concluded that repeated experience of aggression provokes the development of anxiety in male mice. The results suggest that level of anxiety and its behavioral realization depend on duration of aggressive experience and genetic strain.     

The estrogenic arousal of aggressive behavior in female mice

Experiments were conducted to determine the conditions under which estrogen would promote male-like aggressive behavior in female mice. The results of the first experiment showed that most females chronically exposed to testosterone propionate (TP) in adulthood fought, whereas females similarly treated with estradiol benzoate (EB) did not display aggression. Another experiment found that, when either TP or EB was administered on the day of birth, adult females displayed aggression in response to daily EB injections during adult life. Also, the potentiating effect of neonatal hormone exposure declined over the first 12 days postpartum, as 100% of the Day 0, 75% of the Day 6, and 0% of the Day 12 and 18 TP-treated females fought in response to daily injections of 40 μg of EB in adulthood. The final study showed that, under the test conditions employed, the failure of a chronic adult EB regimen to promote aggression was not due to a competing tendency to display female sexual behavior.