Neurogenetics of Social Behavior Sector

SUMMARY OF MAIN RESEARCH RESULTS

NEUROPHYSIOLOGICAL MECHANISMS OF AGONISTIC BEHAVIOR

Data obtained showed that repeated experience of social victories or social defeats in daily agonistic confrontations produced numerous changes in neurochemistry, physiology and behavior of male mice with the alternative types of social behaviors (winners or losers). It has been determined the total activation of dopaminergic systems in winner's brain. Chronic experience of defeats was accompanied by changes in serotonergic and noradrenergic metabolism in limbic brain areas of losers. Significant differences in emotionality, exploratory activity, locomotion, pain sensitivity, ability to demonstrate catatonic immobility reaction, immune responsiveness, alcohol and sexual motivation, reactivity to social pheromonal stimuli as well as to the gastric mucosa damage under social stress were found between the winners and losers. Expression of changes arising under influence of chronic social conflict depends on social type of behavior (aggressive, submissive), strains of mice and on duration of social agonistic experience.

EXPERIMENTAL APPROACH TO THE STUDY ON LEARNED AGGRESSION

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. Relevant situation provokes increases in aggression (boundary aggression). Data obtained testify 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 the winners under influence of repeated experience of aggression. Decrease of mRNA level of catechol-O-methyltransferase gene in the midbrain and increase of mRNA level of dopamine transporter and tyrosine hydroxylase genes in ventral tegmental area were shown in aggressive male mice. The expression of the neurochemical and behavioral changes observed in the winners has been found dependent on the mouse strain and on the duration of their agonistic confrontations. Thus, the sensory contact technique may be used for studying the mechanisms of learned aggression whose examples in the human society may be participation in the war, professional sporting activity, security services, etc., i.e. situations which require the demonstration of aggressiveness for a long period of time.

THE STUDY OF MECHANISMS OF DEPRESSION

It was shown that repeated defeat experiences in daily agonistic confrontations induce dramatic changes in social and individual behavior of submissive mice (losers) of the C57BL/6J strain, which were similar to symptoms of human depression with respect to etiology, susceptibility to treatment, and symptomatology. A remarkable behavioral deficit was found in the losers, who demonstrated only a passive defense after 20 daily defeats tests (T20 losers). This was expressed by the immobile postures during agonistic confrontations, instead of active defense and withdrawal which had predominated in the first confrontations. Losers never demonstrated any aggression to other individuals and displayed a decrease in ambulation in the open field test, as well as an increase in immobility time in Porsolt's test. Development of anxiety estimated by the plus-maze test, as well as disturbance in communicative behavior in the partition test were observed in the losers. Chronic anxiety is assumed to be the main etiological factor in the development of depression in the losers. It is supposed development of anxious depression in the losers. Moreover, highest level of genetically inherent trait anxiety was revealed in mice of C57BL/6J strain in comparison with the others (CBA/Lac and BALB/c). A loss of weight and the enhancement of gastric mucosa damage, as well as a decrease in plasma testosterone level and immune resistance were found in T20 losers. Chronic imipramine and tianeptine treatment prevented the increase of depressiveness as estimated by Porsolt's test. Repeated injections of ipsapirone or buspirone induced anxiolytic effect in T20 losers according plus-maze procedure. Consumption of ethanol improved communicative behavior in the losers. Neurochemical study has revealed alterations in noradrenergic, dopaminergic and serotonergic systems in the brain during the development of depression. Chronic psychoemotional stress of social defeats produced development of experimental anxious depression in male mice similar to this disorder in humans. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels, tryptophan hydroxylase (TPH) and monoamine oxidase A (MAO A) activities, 5-НТ1А receptors in different brain areas were investigated at different stages of development of experimental depression. It has been shown that initial stage (3 days of social stress) is accompanied by increase of 5-НТ level in some brain areas. Decreased 5-HIAA levels in the hippocampus, amygdala and nucleus accumbens were discovered at the stage of forming depression (10 days of social stress). Pharmacological desensitisation and decreased number of 5-НТ1А receptors were shown in frontal cortex and amygdala. At the stage of pronounced depression (20 days of stress), there were no differences in 5-HT and 5-HIAA levels in all brain areas (excluding hypothalamus) of depressive animals. However increased number of 5-НТ1А receptors and decreased affinity in amygdala and decreased TPH and MAO A activities in hippocampus were found in depressive mice. Hypofunction of serotonergic system is suggested at the stage of pronounced depression state in animals. Similar processes had place in brain dopaminergic systems. It is concluded that dynamic changes of brain monoaminergic activities accompany the development of anxious depression in animals. Various parameters of monoaminergic systems are differently changed depending on brain area, mediator system and stage of disorder.