Effect of long-term restraint stress on behavior of female C57BL/6J and CBA/Lac inbred mice. Dispersion and cluster analysis]

An augmented exploratory behaviour and motor activity and diminished anxiety after a restraint stress were found in CBA/Lac female mice [corrected] but not in C57BL/6J ones. In the Porsolt test the result was exactly opposite. A possibility of inherent anxiety-depressive pathological condition in the C57BL/6J mice [corrected] developing under the effect of repeated psychological stress, is assumed.     

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.     

Effect of genotype on the development of aggressive and submissive behavior in the mouse

Aggressive and submissive behaviour was studied in CBA/Lac and C57BL/6J strains of mice during long-term intermale interaction with syngenic partners. It was shown that the aggressiveness of aggressive C57BL/6J animals was more expressive than that of CBA/Lac' ones. The structure of submissive behaviour of this strains' encounters was also significantly different. Prolonged-defeat experience changed the character of submissive behaviour of C57BL/6J, but not of CBA/Lac' ones. Aggression of dominant animals considerably decreased in both strains. It is suggested that CBA/Lac and C57BL/6J mice had different mechanisms of suppression of intermale aggression.     

Experience of defeat increases the susceptibility to catatonic - like state in mice

The ability to develop the catatonic-like state (reflex immobility reaction - RIR) due to stimulation of the skin at the scruff was investigated in mice of two strains — C57BL/6J and CBA/Lac. The total time of immobility and number of paroxysms during test were measured. It has been shown that the number of paroxysms was significantly fewer and the total time of immobility was significantly longer in CBA/Lac strain than in C57BL/6J. In each strain group housed animals as well as submissive ones with successive experience of defeats demonstrated a more expressed immobility than individually housed or aggressive males with successive experience of victories, respectively. Changing the social status in aggressive animals as a consequence of confrontation with aggressive males resulted in the increased immobility in CBA/Lac but not in C57BL/6J mice. The results suggest that the experience of defeat in submissive males is connected with increased ability to develop RIR.     

Extinction of passive avoidance response in various mouse strains

Dependence of the passive avoidance extinction dynamics on a mouse strain was shown. Mice C57BL/6J and AKR/J extinguished more quickly relative to DBA/2J, CBA/Lac and BALB/c, and this extinction was stable. Individual instability of extinction was characteristic of C3H/HeJ mice. Extinction of the passive avoidance in mice CBA/Lac and BALB/c was slower: with a delay in the beginning and prolonged retention of memory trace of the shock exposure. In DBA/2J mice, the extinction was impaired. These data suggest that DBA/2J, CBA/Lac and BALB/c mice constitute groups of risk with high predisposition to impairment of extinction of memory of aversive events, which is thought to be a symptom of a depressive-like state.     

Effect of intranasal administration of dopamine on anxiety and locomotor activity of two lines of mice

Intranasal administration of dopamine (0.3; 3 and 30 microg/kg) on anxious behaviour of mice was studied using elevated plus-maze and open fields tests and the pinch-induced catalepsy on parallel bars test. Dopamine was introduced as nose drops or inhalation of nanoparticles of the compound solution in C57B1/6J and CBA/Lac mice with differences of dopaminergic function features. In our experiment, dopamine had anxiolytic and elevated motor activity effects in C57B1/6J, but not in the CBA/Lac mice. Nose drops were more effective than inhalation; perhaps, it was a more stressful manipulation. Apparently dopamine increased the number of CBA/Lac mice who demonstrated catalepsy and the reflex duration. Indeed, the neurotransmitter is active in different psycho-emotional phenomena.     

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 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

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.     

Response of the serotoninergic brain system to social stress of various duration in male mice C57BL/6J and CBA/Lac]

The effects of social stress caused by experience of defeats in mice during 3 or 10 consecutive days of intermale confrontations on serotonergic brain activity (5-HT, 5-HIAA levels and 5-HIAA/5-HT ratio) in some brain regions of CBA/Lac (CBA) and C57BL/6J (C57) inbred mice have been studied. It was revealed the significant changes in 5-HT methabolism in the brain regions of defeated mice (losers) of CBA strain after 3 intermale confrontations. However, after 10 days of social stress these changes (excluded amygdala) turned to the control measures testifying to the adaptive mechanisms of serotonergic system in CBA losers. In C57 strain, the three-day social stress produced the mild changes in the brain serotonergic activity both quantitatively as well as qualitatively. Nevertheless, losers subjected to ten-day intermale confrontations had more expressed changes in 5-HT, 5-HIAA levels of 5-HIAA/5-HT ratios in the brain regions studied. It seems that long lasting social stress induced the development of disbalance of the brain serotonergic activity in C57 losers: it was shown the hyperactivity in the hypothalamus and hypoactivity in the amygdala and nucl. accumbens. Apparently, this cause leads to the development of the pronounced anxiety shown earlier in this mouse strain.     

Mechanism of the intensification of the immune response to Staphylococcus in mice after the transplantation of primed donor splenocytes

Experiments on CBA, C57Bl/6 mice and (CBA X X C57Bl/6)F1 hybrids were made to study the mechanism of stimulation of the immune response to staphylococci after injection of primed splenocytes. The stimulating action of immune splenocytes was reversed after their in-vitro treatment with anti-immunoglobulin serum and complement. The stimulant effect was also seen in a semi-allogeneic system (adoptive transfer of CBA mice immune cells to (CBA X C57Bl/6)F1 recipients). Preincubation of splenocytes with CBA-anti-C57Bl/6-serum and complement prior to demonstration of antibody-forming cells did not influence their number in the spleen of hybrid recipients injected with immune cells carrying parent genotype but decreased this indicator of the immune response in control mice. It is concluded that stimulation of the immune response to staphylococci after transplantation of primed splenocytes is due to the anamnestic response of donor's cells repeatedly stimulated by antigen in the recipient's host.     

Postradiation volatile secretion and development of immunosupression effectes by laboratory mice with various genotype

The appearance of lines CBA and C57Bl/6 in the urine of mice irradiation volatile excretions with immunosupression property was associated with the violation at mice of ability to immunogenesis. It was established, that immunosupression activity of excretions irradiated mice CBA and C57Bl/6 did not depend on genotip of mice. However, by irradiated mice C57Bl/6 immunosupression components, depressing antibody formation at intact mice, appeared earlier, than at CBA. Immunosypression, limited postradiation volatile secretion in view of depression humoral immune response at intact mice kept for not a long time and mostly expressed on the course 2-3 days after exposition with postradiation secretion.     

Effects of chronic treatment with ipsapirone and buspirone on the C57BL/6J strain mice under social stress

We experimented on inbred C57BL/6J strain mice who experienced social stress caused by defeat in inter-male confrontations for 20 days. From the fifth fight on, some mice were injected with ipsapirone (3 mg/kg), and some with buspirone (1 mg/kg) on a daily basis, for 14 days. Post-treatment behavior was examined in the plus-maze, partition, and Porsolt forced swim test (Porsolt's test). Each of these drugs had anxiolytic effects in the plus-maze, suggesting that they reduce state anxiety. Neither had any effect in the partition test, which provides further support to the hypothesis that normally the C57BL/6J strain mice have a high level of trait anxiety and for that reason they did not respond to the drugs. Chronic treatment with neither drug had any effect in the Porsolt's test. It is proposed that ipsapirone and buspirone fail to alleviate the depressive-like behaviors in the C57BL/6J mice because of a high level of trait anxiety, which might be inherent to this mouse strain.     

Influence of sex and genetic background on anxiety-related and stress-induced behaviour of prodynorphin-deficient mice

The role of dynorphin/kappa opioid receptors in epilepsy and addiction are well accepted, but their function in emotional control is not yet fully understood. Data obtained from different strains of prodynorphin (Pdyn)- and kappa opioid receptor (KOP)-deficient mice do not provide a consistent picture of the functions of Dyn/KOP in anxiety, suggesting the influence of testing conditions and/or genetic background. Therefore, we investigated the behaviour and neurochemistry of male and female Pdyn KO mice on the balb/c and C57Bl/6N background. Consistent with our results obtained from male mice on the C57bl/6N background, we observed a less anxious phenotype in the elevated plus maze, open-field and light-dark test in male mice on the balb/c background. Female mice on the balb/c background also displayed less anxiety like behaviour; however these data reflect high trait anxiety and inter-individual differences. In contrast, female mice on the C57Bl/6N background displayed low trait anxiety and a paradigm-dependent reduction of anxiety. No differences were observed in the forced swim test, while balb/c Pdyn KO mice displayed prolonged immobility in the tail suspension test. In line with our previous results, we observed reduced CRH mRNA in the central amygdala in all groups of mice. In contrast, the recently observed CRH mRNA reduction in the hypothalamic paraventricular nucleus appears restricted to male, but not female mice. Our data support previous data suggesting a pronounced impact of endogenous prodynorphin-derived peptides on anxiety. Moreover, our data support the idea that the less anxious phenotype manifests only at elevated stress levels.     

Interaction of allogeneic lymphocytes and precursor cells during the primary and secondary immune response]

A mixture of lymph node cells from CBA mice and spleen cells from C57Bl/6J mice stimulated by the cheep erythrocytes fro the first or second time was transplanted in the lethally irradiated mice (CBA X C57Bl/6j)Fl. The interaction of allogenic cells during the secondary immune response was accompanied by the complete inactivation of antibody producents. Under the ratio of interacting cell elements 1 : 1-1 : 2, 93-96% of precursor cells and 98% of antibody forming cells were inactivated. Under the ratio 1 : 5, the index of inactivation of precursor cells fell down to 35%. During the primary response, under the ratio 1 : 1, only 20-48% of precursor cells and 68% of antibody forming cells were inactivated. Under the ratio 1 : 2, no inactivation of precursor cells was observed and, under the ratio 1 : 10, the antibody formation was stimulated. Following the delayed by 1-3 days transplantation of CBA lymphocytes, the cooperative effect was registered with respect to the spleen cells from C57Bl/6J mice stimulated by the erythrocytes for the first time. The interaction of allogenic cells resulted in the 3-4-fold increase in the number of antibody forming cells.     

Allogenic inhibition of the stem hematopoietic cells in the bone marrow of adult mice and in the embryonal liver]

The maternal effect was shown to influence the degree of allogenic inhibition of stem hemopoietic cells of the embryonic liver and adult bone marrow in CBA and C57Bl/6 mice. The display of allogenic inhibition of stem cells of the embryonic liver and adult bone marrow proved to be similar in C57Bl/6 mice and dissimilar in CBA.     

Comparative characteristics of the parameters of an aggressive reaction in 2 mouse genotypes

The parameters have been studied of the aggressive reaction of male mice of CBA/Lac and C57BL/6J lines differing by olfactory sensitivity to zoosocial pheromone stimuli. It has been shown that CBA males, characterized by a high olfactory sensitivity, have lower latency of the first attack than C57BL males with low olfactory sensitivity. A prolonged distant exposition to an unknown litter and male appearance lowers the latency of the first attack in mice of the studied lines proportionally to their meanings demonstrated after short time exposition. The number of attacks and total time of attacking is considerably higher in C57BL mice during the whole test period (15 min) than in CBA mice in which aggressivity is already sharply lowered after 5 min of agonistic interactions. The factors are discussed, influencing the parameters of mice aggressive reaction.     

Mapping quantitative trait loci affecting circadian photosensitivity in retinally degenerate mice

It is known that retinally degenerate C57BL/6J (rd/rd) mice have unattenuated circadian photosensitivity. However, the authors have previously found that CBA/J (rd/rd) mice that carry the same rd mutation have attenuated circadian photosensitivity compared to normal CBA/N (+/+) mice. In the present study, a quantitative trait locus (QTL) analysis using C57BL/6J (rd/rd) and CBA/J (rd/rd) mice was conducted in order to identify the genes affecting circadian photosensitivity of the rd mice. As a result, several putative QTLs onthree separate chromosomes (8, 12, 17) were detected, which indicates that circadian photosensitivity in rd mice is altered by multiple genes. Identification of these genes may provide new insights into the understanding of regulation of circadian photoentrainment and sleep-wake disorders.     

Genetic aspects of the reaction of humoral immunity to collagen in humans and animals. Report I. Analysis of polymorphism of autoantibody levels to collagen type I in mice NZB X NZW (F1)

The study of polymorphism of humoral immunoreactions to the type I (AC) collagen in CBA/Lac, C57B1/6-J inbred mice and NZB X NZW (F1) hybrids showed the presence of genetically determined variability of the above mentioned trait. The analysis of intralinear dispersions of AC levels in NZB X NZW (F1) mice revealed sex dimorphism and age variability of the trait. A suggestion was made that sex hormones are important factors in ontogenic formation and modulation of autoimmunity to the type I collagen in NZB X NZW (F1) mice.     

Effect of genotype and day or night time of testing on mice behavior in the light-dark box and the open-field tests

The light-dark box (LDB) and the open-field (OF) tests are widespread experimental models for studying locomotion and anxiety in laboratory rats and mice. The fact that rodents are nocturnal animals and more active at night raises a critical question of whether behavioral experiments carried out in the light phase are methodologically correct. Parameters of behavior of four mouse strains (C57BL/6J, DBA2/J, AKR/J and CBA/LacJ) in the light-dark box and open-field tests in the light and dark phases were compared. No significant influence of the phase of testing on anxiety in LDB and OF tests was revealed. In the OF test CBA mice showed increased locomotor activity, whereas AKR and C57BL/6 mice showed increased defecation in the dark phase. It was concluded that: 1) the phase of testing is not crucial for the expression of anxiety in LDB and OF; 2) the sensitivity to the phase of testing depends on the genotype; 3) the indices of behavior in the genotypes sensitive to the phase of testing (locomotion in the CBA and defecation in the AKR and C57BL/6 mouse strains) are increased in the dark phase.     

Antibodies to catecholamines and serotonin during alcoholic intoxication in animals with different predispositions to the development of experimental alcoholism

Experiments on C57Bl/6, CBA and DBA/2 mice characterized by different preferences for ethanol have shown that during chronic administration of alcohol to animals with natural ethanol motivation (strain C57Bl/6) the level of antibodies to catecholamines and serotonin was increased on the 3rd month of ethanol intoxication, with the voluntary alcohol consumption in mice decreased by this time. On the contrary in mice rejecting alcohol (strains DBA/2, CBA) no antibodies to catecholamines and serotonin have been found.