[Development of movement disorders in DBA/2J male mice under repeated experience of aggression].

Changes in the behavior of DBA/2J mice after gaining repeated experience of aggression have been investigated. It was shown that the long-term experience of aggression led to development of hyperactivity estimated as increased motor activity in different tests: open field, elevated plus maze and during testing of reaction to a novelty. Symptoms of attention deficit estimated in the "partition" test as a reduction of the communicativeness and the lack of reaction to unfamiliar partner were noticed. Appearance of a large number of hyperkinesis manifested most often in the form of sudden involuntary head movements (jerks) was observed in the behavior of aggressive males during agonistic interactions. Most of the changes in the behavior of DBA/2J mice differed significantly from previously detected in the behavior of aggressive mice of C57BL/6J and CBA/Lac strains, suggesting a significant contribution of heredity that determines the features of behavioral disorders that occur under the influence of long-term experience of aggression. Similarity of symptomatics of movement disturbances in mice and in humans with some neurological diseases is discussed.

[Pro-aggressive effect of diazepam in male mice with repeated experience of aggression].

Previous studies have reported that repeated experience of aggression is attended with the development of increased anxiety in male mice. The paper aimed to investigate effect of anxiolytic, diazepam, on the level of anxiety and aggression in these animals. The drug was chronically administrated for two weeks at the process of aggression experience acquisition. It was shown that diazepam decreased anxiety but didn't influence aggression level assessed by total time of attacks. However, diazepam decreased demonstration of aggressive grooming in part of aggressive males. Group of diazepam-treated aggressive males which displayed aggressive grooming didn't differ in level of anxiety and aggression in saline-treated male mice. Diazepam had anxiolytic and pro-aggressive effects in male mice without demonstrating aggressive grooming. Thus, we can conclude that anxiolytic effect of diazepam is accompanied with increased aggression as side effect in some male mice which have repeated experience of aggression.

[Secretion of proteolytic enzymes by three phytopathogenic microorganisms].

Serine proteinases from three phytopathogenic microorganisms that belong to different fungal families and cause diseases in potatoes were studied and characterized. The oomycete Phytophthora infestans (Mont.) de Bary and the fungi Rhizoctonia solani and Fusarium culmorum were shown to secrete serine proteinases. An analysis of the substrate specificity of these enzymes and their sensitivity to synthetic and protein inhibitors allowed us to refer them to trypsin- and subtilisin-like proteinases. The correlation between the trypsin- and subtilisin-like proteinases depended on the composition of the culture medium, particularly on the form of the nitrogen source. A phylogenetic analysis was carried out. In contrast to basidiomycetes R. solani, ascomycetes F. culmorum and oomycetes P. infestans produced a similar set of exoproteinases, although they had more distant phylogenetic positions. This indicated that the secretion of serine proteinases by various phytopathogenic microorganisms also depended on their phylogenetic position. These results allowed us to suggest that exoproteinases from phytopathogenic fungi play a different role in pathogenesis. They may promote the adaptation of fungi if the range of hosts is enlarged. On the other hand, they may play an important role in the survival of microorganisms in hostile environements outside their hosts.

[Attenuating effect of sucrose solution intake on increase in aggression produced by fighting deprivation in male mice with repeated experience of victories].

It was found earlier that winners (male mice with experience 20 daily victories in aggressive agonistic encounters) showed enhanced aggression after a 2-week no-fight period, compared to their respective levels of aggressive behavior before the fighting deprivation. In this work we showed that sucrose solution intake in the deprivation period attenuated the level of post-deprivation aggression and decreased anxiety in such animals. Negative correlations were found between sucrose intake and aggression level. Putative mechanisms of attenuating sucrose effect on aggressive behavior are discussed.

[Decrease in sucrose solution consumption by CBA/Lac male mice under chronic social stress].

The influence of repeated experience of social defeats in daily agonistic interactions on voluntary consumption of 1% sucrose solution supplemented with vanillin (0.2%) was studied in male mice of CBA/Lac strain with genetic predisposition to catalepsy as compared to depression-predisposed C57BL/6J mice. Intact mice of both strains prefered sucrose solution to water under conditions of two-bottle free choice. Sucrose solution intake was shown to decrease in losers of both strains exposed to social confrontations as compared to controls. It was suggested that the high level of anxiety revealed in mice of both strains can be the determining factor of the decrease in sucrose solution consumption under conditions of chronic social stress.

[The influence of cultural medium composition on the proteolytic enzyme secretion of fungus Rhizoctonia solani].

It was shown that change of medium growth composition of photopathogenic fungus Rhizoctonia solani Kühn, especially accessible sources of nutrition, leads to change of both quantity of produced proteinases and their action specificity. The mineral source of nitrogen suppressed the fungus proteinase secretion on cultivation medium containing potato thermostable proteins but an organic source of nitrogen accelerated mycelium growth and increased proteinase secretion. On the basis of an analysis of a fungus extracellular proteinase substrate-specificity, it is established that the presence of thermostable proteins of a potato in the cultural liquid induces the secretion of trypsin-like proteinases mainly, and the addition of yeast extract to this growth medium induces the secretion of subtilisin-like ones, thus suppressing the trypsin-like enzymes production. This fact can indicate that mycelium of fungus R. solani loses pathogenic properties and becomes saprophytes when the growth medium was enriched by an organic source of nitrogen.

[Effect of sodium valproate on aggressive behavior of male mice with various aggression experience].

Sector of Social Behavior Neurogenetics, Institute of Cytology and Genetics, Siberian Branch, Effects of sodium valproate on the aggressive behavior of male mice with 2- and 20-day positive fighting experience have been studied. It is established that valproate administered in a singe dose of 100 mg/kg has no effect on the behavior of male mice with a 2-day experience of aggression. The treatment of mice with 300 mg/kg of valproate significantly decreased the level of aggressive motivation and the percentage of animals demonstrating attacks and threats. In male mice with a 20-day experience of aggression, valproate decreased the time of hostile behavior in a dose-dependent manner. Valproate in a single dose of 300 mg/kg significantly decreased the level of aggressive motivation, but also produced a toxic effect, whereby 73% of aggressive males demonstrated long-term immobility and 45% exhibited movement abnormalities (falls) upon the treatment. It is suggested that changes in the brain neurochemical activity, which are caused by a prolonged experience of aggression, modify the effects of sodium valproate.

[Effect of positive and negative social experiences on sucrose solution intake by male mice].

Hedonic reactions to various rewards play a key role in various forms of motivated behavior. The influence of repeated experience of social victories or defeats in daily agonistic interactions between male mice on voluntary consumption of 1% sucrose solution supplemented with vanillin (0.2%) was studied. Intake of sucrose solution was shown to be decreased in the winners and losers exposed to social confrontations as compared with the controls. Three days of deprivation restored the intake of sucrose solution to the control level in the winners and failed to restore the baseline intake in the losers. The results imply that similar reaction of animals to a hedonic non-drug reinforcer may have different motivational origin depending on positive or negative social experience.

[The study of exploratory behavior in CBA/Lac male mice under influence of positive and negative social interactions].

The exploratory activity towards a new object placed in the home cage was studied in CBA/Lac male mice after their repeated daily social victories and defeats. After 10 daily social defeats, submissive mice displayed a significantly declined exploration of a new object, whereas aggressive mice with experience of 10 daily victories expressed only a mild decrease in exploratory activity (as compared to control). Twenty daily social defeats almost completely abolished exploratory behavior in submissive mice, whereas 20 daily victories resulted in the increased exploration of a new object in aggressive mice. It is suggested that repeated social defeats associated with the negative psychoemotional state lead to the development of a pronounced exploratory motivational deficit. On the other hand, the experience of repeated daily aggression forms the enhanced motivational excitement that prevents a relevant response to a neutral stimulus.

[Influence of experimental context on the development of anhedonia in male mice exposed to chronic social stress].

Consumption of 1% sucrose solution supplemented with 0.2% vanillin was studied in two experimental contexts in male mice living under chronic social stress induced by daily experience of defeats in agonistic interactions and leading to development of depression. In the first experiment, vanillin sucrose solution was made available as an option along with water during 10 days for mice living in group home cages. Then the mice were subjected to repeated social defeat stress and during exposure to stress they were provided with both vanillin sucrose solution and water using a free two-bottle choice paradigm. In the other experiment, vanillin sucrose solution was first offered to mice after 8 days of exposure to social defeat stress. Males familiar with vanillin sucrose solution showed vanillin sucrose preference while experiencing defeat stress: consumption of vanillin sucrose solution was about 70% of total liquid consumption. However, the consumption of vanillin sucrose solution per gram of body weight in mice exposed to social stress during 20 days was significantly lower than in control males. In the second experiment, males after 8 days of social defeat stress were found to consume significantly less vanillin sucrose solution as compared to control males. On average, during two weeks of measurements, vanillin sucrose solution intake was less than 20% of total liquid consumption in males. Consumption per gram of body weight also appeared to be significantly lower than in control group. The influence of experimental context on the development of anhedonia measured as a reduction of sucrose solution intake by chronically stressed male mice is discussed.

[Extracellular proteinases from the phytopathogenic fungus Fusarium culmorum].

The growth of Fusarium culmorum fungus on a medium containing thermostable proteins from potato tubers was accompanied by the production of proteinases, exhibiting activity over a broad pH range (from 6.0-10.0). When studied by SDS-PAGE in the presence of beta-mercaptoethanol, extracellular proteinases were represented by at least five species with a molecular weight of 30-60 kDa. Inhibitor analysis and studies of enzyme activities with synthetic substrates demonstrated that the culture liquid of Fusarium culmorum contained serine proteinases of various classes. The amount of subtilisin-like proteinases was the highest. A near-complete inhibition of the enzymes was caused by proteinaceous proteinase inhibitors from potato tubers. These data suggest that proteinases of the phytopathogen Fusarium culmorum serve as a metabolic target for natural inhibitors of potato proteinases.

[Interaction between proteinases secreted by the fungal plant pathogen Rhizoctonia solani and natural proteinase inhibitors produced by plants].

The fungal plant pathogen Rhizoctonia solani Kuhn. grown in a medium containing thermostable potato tuber proteins produced proteinases active at moderately alkaline pH values. Electrophoretic analysis in polyacrylamide gel with SDS and copolymerized gelatin showed that the extracellular proteinase complex contained four components that differed in molecular weight. Studies on the action of the exoenzymes on various synthetic substrates indicated that the culture liquid of R. solani contained mainly trypsin-like proteinases. The exoproteinase activity was virtually completely suppressed by trypsin inhibitor proteins isolated from potato tubers and seeds of various legume species. The results suggest that the extracellular proteinases produced by R. solani play a significant role in attacking plant tissue, and natural inhibitors contribute to the protection of Solanaceae and Leguminosae from this fungal pathogen.

[Impaired social recognition in male mice with repeated experience of aggression].

Social recognition is crucial for many aspects of animal behavior in stabilized population. Preliminary data proposed impairment of social recognition in male mice with long experience of aggression. To check this hypothesis, experiments with male mice with different aggressive experience (during 2 and 20 days) were performed. Two types of losers were used as partners: losers with active defense reactions and losers displaying submissive postures. The enhanced aggressive motivation was found in both groups of aggressors. Mice with short aggressive experience demonstrated intensive attacks toward the active losers and decreased aggression directed to submissive losers. Mice with long aggressive experience did not change their behavior depending on a type of the partner and displayed a high level of aggression as a result of dominant aggressive motivation and impaired social recognition.

[Lorenz was right, or does aggressive energy accumulate?]. / A Lorents-to byl prav! ili nakaplivaetsia li agressivnaia énergiia?

Evidence supporting the fact that inherited mechanisms of regulation of aggressive behavior as a result of a repeated experience of aggression ending in victories are transformed into pathological mechanisms based on accumulation of neurochemical shifts in the brain, enhancing aggressiveness, and forming aggressive motivation in aggressive winners. This confirms the concept by Lorenz on the existence of a mechanism (but not instinct) of a spontaneous accumulation of aggressive energy that needs a discharge and formation of permanent attraction to manifestation of aggression.

[Genetic control of the serotonin content in the blood of mice]. / Geneticheskii kontrol' soderzhaniia serotonina v krovi u myshei.

The Griffing's method of diallel analysis and hybridological analysis were used to study inheritance of serotonin level in blood in mice. Effects of general and specific combining ability proved to be highly significant, the former being more pronounced. Results of hybridological analysis allowed to suggest a simple genetic control involving a small number of genes. A conclusion is drawn that the level of serotonin was mainly determined by additive affects of genes.

[Effect of the genotype on the serotonin and 5-hydroxyindoleacetic acid content in different sections of the mouse brain]. / Vliianie genotipa na soderzhanie serotonina i 5-gidroksiindoluksusnoi kisloty v razlichnykh otdelakh golovnogo mozga myshei.

The levels of serotonin and 5-hydroxyindoleacetic acid contents were estimated in hypothalamus, hyppocampus and midbrain of inbred mice of 12 strains. The levels of serotonin and its metabolite in various parts of brain representing different links of its serotoninergic system were shown to be genetically determined. The correlation analysis revealed that there were two, relatively autonomous genetic systems controlling biosynthesis and catabolism of serotonin in brain.

[Genetic control of the tissue concentration of serotonin in mice]. / Geneticheskii kontrol' tkanevogo soderzhaniia serotonina u myshei.

Brain stem, stomach and blood serotonin contents were studied in inbred mice of eight strains. The serotonin level in brain and in peripheral tissue is genetically determined. There was no correlation between the serotonin levels of brain, blood and stomach. This suggests a different genetic regulation of serotonin metabolism in the central nervous system and in the gastrointestinal tract.

[Inheritance of the serotonin level in 1st-generation mice from crosses with different inbred strains]. / Nasledovanie urovnia serotonina u myshei pervogo pokoleniia pri skreshchivanii raznykh inbrednykh linii.

The level of serotonin content in brain stem and stomach was studied in the first generation of different combinations of inbred mice strains. The serotonin level was shown in these tissues to be inherited differently. Heterosis was observed in the gastro-intestinal tract. Serotonin brain level depends on strain combinations in crosses.

[Changes in the expression of monoaminergic genes under the influence of repeated experience of agonistic interactions: from behavior to gene]. / Izmeneie ékspressii monoaminergicheskikh genov pod vliianiem povtornogo opyta agonisticheskikh vzaimodeistvii: ot povedeniia k genu.

The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergetic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic system and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the catechol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.

[Neurobiological correlates premeditated (learned) aggression: seeking new experimental approaches]. / Neirobiologicheskie korreliaty prednamerennoi (obuchennoi) agressii: poiski éksperimental'nykh podkhodov.

Theoretical possibility of experimental modeling of learned (premediated) aggression developing in human after experience of aggression is considered. The sensory contact technique increases aggressiveness in male mice and allows aggressive type of behavior to be formed as a result of repeated experience of victories in daily agonistic confrontations. Some behavioral domains confirm the development of learned aggression in males similar to those in humans. The features are: repeated experience of aggression reinforced by victories; elements of learned behavior after period of confrontations; intent, measured by increase of the aggressive motivation prior agonistic confrontation; decreased emotionality estimated by parameters of open field behavior. Relevant stimuli provoke demonstration of aggression. This review summarized data on the influence of positive fighting experience in daily intermale confrontations on the behavior, neurochemistry and physiology of aggressive mice (winners). This sort of experience changes many characteristics in individual and social behaviors, these having been estimated in different tests and in varied situations. Some physiological parameters are also changed in the winners. Neurochemical data confirm the activation of brain dopaminergic systems and functional inhibition of serotonergic system in winners under influence of repeated experience of aggression. The expression of the neurochemical and behavioral changes observed in winners has been found dependent on the mouse strain and on the duration of their agonistic confrontations. Similarities in mechanisms of learned aggression in humans and mice are considered.