[Effect of a single severe stress on behaviour of males and females in the mouse inbred strains CBA/Lac and C57BL/6J].

The effect of single severe stress in the form of forced swimming on the behavior of males and females in the mouse inbred strains CBA/Lac and C57BL/6J were examined in the open field test. Measurements were carried out within two hours after the stress exposure (Trial 1) and repeated 2 hours thereafter (Trial 2). Intact males and females of the both mouse strains which tested in the open field twice too were used as control. An increased latency was found until first escape from the center both in males and females of the CBA/Lac strain within two hours after the end of forced swimming. This parameter was still high in females in the Trial2. Four out of seven behavior parameters were changed in females of the C57BL/6J strain two hours after the stress exposure, but their behavior was similar to control in the Trial 2. The males of the C57BL/6J strain demonstrated the least changed behavior in the open field test after the stress exposure with the exception of increased number of grooming in the Trial 1. Further on, a detailed analysis of repeated testing in the open field within intact and stressed mice of both strains was performed. This comparison allowed revealing hereditary and gender peculiarities in the mouse behavior after single severe stress exposure. The results are discussed in respect to the possible genetically inherent increased traitanxiety in females of C57BL/6J strain and the state of anxiety in females of CBA/Lac strain.

[Dynamic changes of brain serotonergic and dopaminergic activities during development of anxious depression: experimental study]. / Dinamicheskue izmeneniia serotonergicheskoi i dofaminergicheskoi aktivnosti mozga v protsesse razvitiia trevozhnoi depressii: éksperimental'noe issledovanie.

Chronic psychoemotional stress of social defeats produces development of experimental anxious depression in male mice similar to this disorder in humans. 5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different brain areas were investigated at different stages of development of experimental disorder. It has been shown that initial stage (3 days of social stress) is accompanied by increase of 5-HT 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-HT1A-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-HT1A-receptors and decreased affinity in amygdala and decreased TPH and MAOA 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.

[Involvement of kappa-opioid receptors in mechanisms of aggressive and submissive types of behavior in male mice]. / Vovlechenie opioidnykh kappa-retseptorov v mekhanizmy formirovaniia agressivnogo i submissivnogo tipov povedeniia u samtsov myshei.

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.

[Is dehydroepiandrosterone sulfate an anxiolytic agent?]. / Iavliaetsia li degidroépiandrosteron-sulfate anksioliticheskim agentom?

Effects of dehydroepiandrosterone sulfate (DHEAS, 30 mg/kg, i.p., 4 and 28 hours after the injection) were studied in CBA/Lac male mice different in the level of anxiety resulting from repeated social victories (winners) or social defeats (losers) in 10 daily agonistic confrontations. The losers demonstrated high level of anxiety estimated by the "partition" test. The DHEAS and saline injections had different effects on winners, losers, and intact mice. DHEAS prevented the development of anxiety in losers 28 hours after the injection. In these experimental conditions DHEAS exerted no effect on winners. It was concluded that the DHEAS effect depends on the psychoemotional state of an animal. The anxiolytic effect of the exogenous DHEAS may be also characteristic of the endogenous hormone secreted by the adrenal glands and in the central nervous system.

[Modifying effect of the repeated experience of agonistic confrontations on effect of naltrexone in male mice]. / Modifitsiruiushchee vliianie povtornogo opyta agonisticheskikh vzaimodeistvii na éffekty naltreksona u samtsov myshei.

In mice with different experience of agonistic confrontations: victories or social defeats during 3 and 10 days (T3 and T10 winners and T3 and T10 losers, resp.), T10 winners displayed a lesser aggression and a more hostile behaviour than T3 winners. Naltrexone dose-dependently decreased attacks in the T3 winners and did not affect aggressive grooming, diggings, autogrooming, and exploratory activity. Naltrexone was ineffective in T10 winners. The naltrexone effects were similar in T3 and T10 losers and its high and low doses contrarily affected different parameters of submissive behaviour. The repeated experience of agonistic confrontations seems to modify the naltrexone effects depending on a neurochemical background, differing in winners and losers.

[The determination of the parameters of anxiety in C57BL/6J, CBA/Lac and BALB/c mice under the influence of a serotonin C1A receptor agonist [correction of antagonist]. / Vyiavlenie parametrov trevozhnosti u myshei linii C57BL/6J, CBA/Lac i BALB/c pod vliianiem agonista serotoninovykh retseptorov C1A.

Three strains of inbred mice, C57BL/6J (C57), CBA/Lac (CBA), and BALB/c (BALB) were examined in the elevated plus-maze after the injection of an anxiotropic drug, a 5-HT1A agonist ipsapirone (3 mg/kg; i.p.; 30 min). Treatment with ipsapirone had different anxiogenic effects on the behavior of mice in accordance with their genotype. In C57 mice the drug produced a significant decrease in the percentage of the open-arm time and the number of open-arm entries as well as in the number of full entries (when an animal was between the half and the end of an open-arm) and in the number of head dippings. Besides; the number of C57 mice which performed full entries after the ipsapirone injection decreased. In CBA mice ipsapirone reduced the number of enclosed-arm entries, the number of the passages from one enclosed arm to another and the number of head dippings. Only the number of passages dropped in BALB mice after the drug injection. Probably, just these parameters reflect anxiety in mice of the genotypes under study. It was suggested that the sensitivity of 5-HT1A receptors in C57 mice is the highest.

[The effect of central serotonin administration on the neurogenic damage to the gastric mucosa due to chronic social stress in inbred mice]. / Vliianie tsentral'nogo vvedeniia serotonina na neirogennye povrezhdeniia slizistoi obolochki zheludka, vyzvannye khronicheskim sotsial'nym stressom, u inbrednykh myshei.

A reiterated negative experience of intermale confrontations for 3 and 10 days resulted in aggravation of neurogenic ulceration of gastric mucosa in defeated males from all strains of mice under study, the number of mucosa erosions being 2-3-fold greater than in winners or control animals. Administration of serotonine into the lateral ventricles increased the number of erosions in intact mice of all genotypes. In experimental groups, a considerable diversity was found in respect to the effects of exogenous serotonine on the gastric mucosa. Following 10 days of the stress, both in winners and losers, a decrease of the gastric mucosa sensitivity to central serotonine was revealed.

[Effect of the brain 5-HT2 receptor blockade on gastric mucosa damage caused by social stress in males of two mouse strains]. / Vliianie blokady 5-HT2-retseptorov mozga na povrezhdenie slizistoi obolochki zheludka, vyzvannoe sotsial'nym stressom u samtsov myshei dvukh linii.

Mice-losers in social conflicts had an increased number of haemorrhages and erosions in gastric mucosa as compared with the control and winners-mice. Administration of ciproheptadine and/or ketanserin enhanced the neurogenic gastric damage both in the winners and in control mice. The CBA strain mice were more sensitive to the damaging effects of the drugs than the C57-strain winners. The experience of social confrontations seems to change the gastric mucosa condition and to modify the mucosa response to the brain serotonine receptor blockade, depending on the social confrontations outcome and the animals' genotype.

[Differences in the effects of naltrexone on the communicative and aggressive behaviors of subjects with different experiences of social conquests]. / Razlichiia v éffektakh naltreksona na kommunikativnoe i agressivnoe povedenie u osobei s razlichnym opytom sotsial'nykh pobed.

The authors studied the effect of naltrexone (0.25 and 1.0 mg/kg, intraperitoneal injection) on the communicative and aggressive behavior of male C57BL/6J mice with experience in triumphs in 20 tests (victors) and of mice without such experience (novices). The level of communicativeness and aggression at the first confrontation was more marked in novices than in victors. In the novices 0.25 mg/kg naltrexone selectively reduced communicativeness and in a dose of 1.0 mg/kg shortened the sum time of the aggressive attacks, increasing in this case the time of aggressive grooming. In the victors naltrexone in both doses had no effect on the communicative behavior and period of aggressive grooming but increased the duration of the attacks depending on the dose. In both groups naltrexone increased the number of subjects which demonstrated aggressive attacks and reduced the frequency of aggressive grooming. It is concluded that the state of opiate receptors changes under the effect of repeated experience in the triumph of social confrontations.

[The effect of the repeated experience of victories and defeats in social conflicts on the function of the brain serotoninergic system in male mice]. / Vliianie povtornogo opyta pobed i porazhenii v sotsial'nykh konfliktakh na sostoianie serotoninergicheskoi sistemy golovnogo mozga samtsov myshei.

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels, tryptophan hydroxylase (TPH) activity, and 5-HT1A receptor binding were studied in brain areas of male mice after repeated experience of victories (winners) and defeats (losers) in daily male confrontations. A decrease in the TPH activity in midbrain and its decrease in hypothalamus were shown in winners in comparison with controls. The victory experiences were accompanied by a pronounced increase of Bmax of 5-HT1A receptors in the frontal cortex and decrease of Kd in the hypothalamus. Repeated defeats in social confrontations were accompanied by an increase in 5-HT level in the amygdala and increase of 5-HIAA/5-HT index in the hippocampus in comparison with controls. A decrease of Bmax in the hypothalamus and of Kd of 5-HT1A receptors both in the frontal cortex and hypothalamus was shown in losers as compared to controls. An increase in TPH activity under the influence of repeated defeats was shown in striatum and hypothalamus. The obtained evidence point to specific changes in serotonergic activity which characterize aggressive or submissive types of social behaviour, and unspecific changes which are similar in winners and losers and are likely to be induced by social stress.

[Poststress lesions of the gastric mucosa in inbred mice after the peripheral administration of cyproheptadine and propranolol]. / Poststressornye porazheniia slizistoi obolochki zheludka inbrednykh myshei posle perifericheskogo vvedeniia tsiprogeptadina i propranolola.

Intraperitoneal administration of 5-HT2-receptor blocking agent ciproheptadine abolished the protective effect on stress-induced damage of gastric mucosa in male mice, while propranolol depresses this protective effect. Propranolol prevented a damaging effect of serotonine on gastric mucosa. Consequences of emotional stress on gastric mucosa seem to be realised through different types of serotoninergic receptors.

[The effect of the prolonged experience of aggression and subordination on the adrenal cortical and androgenic functions of inbred male mice]. / Vliianie dlitel'nogo opyta agressii i podchineniia na adrenokortikal'nuiu i androgennuiu funktsii samtsov inbrednykh myshei.

Repeated experience of aggression and submission in daily agonistic confrontations differently changed stress response in winners and losers of CBA/Lac and C57BL/6J strains. Experience of defeats was accompanied by expressed decrease of testosterone level in losers. Number of hemorrhages and erosions was significantly more in losers when compared to winners. Some strain differences in stress reaction were found in winners and losers as compared to controls.

[The participation of serotonin S2 receptors in realizing the effects of stress on ulcer formation in the gastric mucosa of inbred mice]. / Uchastie serotoninovykh S2-retseptorov v realizatsii éffektov stressa na iazvoobrazovanie v slizistoi zheludka inbrednykh myshei.

Significant interstrain differences in intensity and character of changes in gastric mucosa induced by affecting the serotoninergic system, were found. The main mechanism of stress-induced stomach ulceration was found to involve brain serotonin in central regulation of the stomach blood flow. Use of exogenic amine and its precursor corroborated the serotonin-dependent ulceration of the stomach in mice.

[A comparison of the effects of cyproheptadine and propranolol on the development of poststressor lesions of the gastric mucosa in inbred mice]. / Sopostavlenie éffektov tsiprogeptadina i propranolola na razvitie poststressornykh porazhenii slizistoi zheludka u inbrdnykh myshei.

The effects of central cyproheptadine and propranolol were virtually the same but differed in their intensity. Differences between genotypes were shown to be able to determine the differences in effects of the blocking agents on different kinds of stress-induced stomach damage. The data obtained suggest that genotypic properties of the serotoninergic system can interfere considerably with the reactions of the stomach mucosa to emotional stress.

[Central serotonin administration and post-stress damage of the gastric mucosa in inbred mice during various seasons]. / Tsentral'noe vvedenie serotonina i poststressornye povrezhdeniia slizistoi obolochki zheludka myshei inbrednykh linii v raznye sezony.

The severity of neurogenic damage to the gastric mucosa (GM) induced by emotional stress (ES) in administration of serotonin or its precursor in biosynthesis--5-hydroxytryptophan into the lateral ventricle of the brain was studied in experiments on mice of inbred strains. The development of lesions in the GM in the form of erosions and hemorrhages proved to be dependent on many factors, first of all on the time of administration of the preparations--before or after ES. The effect of 5-hydroxytryptophan on the formation of GM stress damage was less marked than that of serotonin. The intensifying effect of exogenous serotonin on post-stress GM damage was mainly manifested in the spring, which is associated with ES induced activation of the brain serotonergic system. The effect of exogenous serotonin on the degree of the neurogenous damage to the GM caused by ES is determined to a great measure by the genotype differences in the sensitivity of the central serotonergic mechanisms to the stimulating effect.

[Genotypic differences in the reactivity of the hypophyseo-adrenal system and the resistance of mice to cooling]. / Genotipicheskie razlichiia v reaktivnosti gipofizarno-nadpochechnikovoi sistemy i ustoichivosti myshei k okhlazdeniiu.

The response of pituitary-adrenal axis (non-specific stress reaction) and body temperature change (specific reaction to cold) to mild and extreme cold was studied in ten mice strains. Genotypic systems controlling the activity of pituitary-adrenal axis under the cold of various intensity seem to be different. It is possible that the extent of decrease in body temperature under the cold of various intensity is determined by the same hereditary mechanisms. It was shown that the considerable phenotypic variability in response of pituitary-adrenal axis and body temperature depends on environmental conditions as well, i.e. on the intensity and duration of cold stress. Significant variability in the survival under cold conditions in different mice strains and the important role of specific reaction to forecast of resistance to cold were discussed.

[Genetic and seasonal characteristics of the effect of stress on pain sensitivity in mice]. / Geneticheskie i sezonnye osobennosti vliianiia perenesennogo stressa na bolevuiu chuvstvitel'nost' myshei.

The role of genetic and seasonal factors in stress-induced changes of pain sensitivity, evaluated by latency in hot plate test was studied. Significant interstrain differences in restriction effect on pain sensitivity was established. Analgesia, hyperalgesia or lack of influence on pain sensitivity in mice of different strains was observed in response to emotional stress. Interstrain differences in seasonal variance of stress-induced changes in pain sensitivity were shown. It is suggested that changes in pain sensitivity of mice after restriction are season-dependent and controlled by hereditary mechanisms.

[Interaction of genetic and environmental components in the determination of tryptophan hydroxylase activity in the mouse brain in stress]. / Vzaimodeistvie geneticheskoi i sredovoi komponent v determinantsii aktivnosti triptofangidroksilazy v mozge myshei pri stresse.

The interaction between genetic and environmental components of phenotype variety in the response to cold and emotional stress of the brain serotonin system was studied in 11 inbred strains of mice. It was shown that the variety in the degree of tryptophan hydroxylase activity's changes under stress are mainly due to the genotypic differences. The presence of different genotypic systems controlling the activity of tryptophan hydroxylase under basal conditions and under stress was revealed. Differences in hereditary mechanisms determining the tryptophan hydroxylase reactions to different kinds of stress were noted.