The development of pathological forms of behavior in submissive male C57BL/6J mice during agonistic zoosocial interactions. A possible model of depression?

It is shown that a long experience of defeats in daily zoosocial collisions (ZC) elicits changes in the structure of submissive behaviour. Male mice of C57BL/6J line after 20 defeats demonstrated poses of passive subordination instead of active defence and run away which they manifested in the first ZC. Moreover, new immobile poses appeared which were rare in the first ZC. Submissive animals (CA) demonstrated a decrease of travels in the open field test and an increase of immobility time in the Porsolt test. Chronic administration of imipramine (10 mg/kg, i.p., twice a day during two weeks against the background of repeated ZC) prevented an increase of depressivity, estimated in Porsolt test. Changes were noted in the content of serotonin and 5-HIAA in some brain structures of subordinated mice in comparison to control animals (five days of isolation). The data are discussed from a position of the development of depression in SA of C57BL/6J line as a result of a long nonavoided zoosocial stress.     

Morphological and cytofluorometric study of the giant cells of the trophoblast of the common vole]

The primary and secondary giant cells of trophoblast in placenta Microtus arvalis were studied. The giant polyploid nuclei are formed in result of series of successively proceeding endomitotic polyploidization of chromosomes. Two stages of endomitosis are described: endointerphase with the uniform net of thin chromatin threads and the stage when small round or rod-shaped paired chromosomes gather mostly under the nuclear membrane. Great number of round, oval, and complex-shaped nucleoli may be seen in nuclei during both stages of endomitosis, the number growing during polyploidization. The morphology of the chromosome-nucleolar apparatus involves peculiarities of the polyploidization mechanism in placenta Microtus arvalis trophoblast. Endomitosis occurs both in low and high-polyploid nuclei. Cytofluorometric determination of the DNA amount in nuclei polyploid nature. The degree of polyploidy of the trophoblast giant cells nuclei during terminal differentiation of placenta corresponds to 128c-512c, and some nuclei contain the DNA amount corresponding to 1024 and 2048 chromosomal sets. The cause of origin of the polyploid cells in trophoblast of rodents placenta is discussed.     

Effect of dansylcadaverine on the epidermal growth factor-stimulated phosphorylation of uridine

The increase of uridine phosphorylation during the first hour after epidermal growth factor (EGF) stimulation (1.25 nM) of Swiss 3T3 cells is completely blocked by 100 microM dansylcadaverine (DC). Lack of the effect of DC on uridine transport, uridine kinase activity in cell homogenate, intracellular ATP concentration and plasma membrane permeability for phosphorylated uridine derivatives makes it possible to propose the inhibition by DC (100 microM) of the activated state of uridine kinase. The rapidity of the inhibition of EGF effect and the lack of influence of DC (in tested concentration) upon the clustering of EGF-receptor complexes, rate of their internalization (Sorkin, 1985; Nikol'ski? et al., 1987) and pH value of intracellular compartments (Sorkin et al., 1985; Teslenko et al., 1986) may suggest an association of DC inhibitory action with blocking of some steps of the receptor mediated endocytosis. Accumulation of DC in cell membranes, rather than in intracellular compartments with acidic pH, is a necessary factor for its blocking effect. Possibilities of DC action through the influence on calmodulin-dependent proteins or EGF-induced cell protein phosphorylation are discussed.     

The neurochemical control of aggression and submission]

Neurochemical mechanisms of agonistic behaviour in different models of aggression are discussed. The effects of aggression and submission experience in 10 mice intermale confrontations under conditions of sensory contact on the levels of brain neurotransmitters and their metabolites were investigated in 7 brain areas. The values obtained in aggressive and control, or submissive and control, animals were compared. In this comparison neurochemical alterations specific for aggressive or submissive behaviours, or nonspecific became apparent. The long experience of victories leads to activation of dopaminergic system through DA catabolism which leads to DOPAC formation. The long experience of defeats increases the 5HT metabolism and decreases NA level in some brain areas. The dopaminergic system of Nucleus accumbens and midbrain are nonspecifically activated in both aggressive and submissive animals. The investigation of values obtained in animals with conversion of behavioural type (after defeat of previously aggressive animals and/or display of aggressive reaction by previously submissive mice) allowed to find many significant differences between aggressive, submissive and "converted" males; in particular the amygdala is the site of opposite changes in 5HT system during inversion of aggressive or submissive behaviours. The above data evidence for the specific role of transmitter systems and brain structures in maintaining or inversion of different types of agonistic behaviour.     

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.     

The relation of tryptophan hydroxylase activity in the brain and the manifestation of catalepsy in mice

Pinch-induced catalepsy and thyptophan hydroxylase (TPH) activity in striatum and midbrain were determined in male mice of 6 inbred strains. Pronounced catalepsy was found in the only mice strain--CBA. TPH activity in midbrain and especially in striatum of CBA mice was higher than in the strains, which did not display catalepsy. The experimental situation, which promotes the development of highly aggressive CBA males, caused a decrease in TPH activity in striatum and these mice did not express genetic predisposition to catalepsy. The results indicate that TPH activity in striatum is involved in the mechanism of catalepsy in mice.     

Na+,K(+)-ATPase activity in human colorectal carcinoma

Na+,K(+)-ATPase activities in macroscopically unchanged mucosa (conditionally normal tissue) and human colorectal carcinoma (mainly low-grade and moderately differentiated adenocarcinomas) have been investigated. Microsomal fractions are similar by dimensions of the membrane fragments detected by photon correlation spectroscopy analysis. The activation optima under digitonin pretreatment of the membrane fractions differ significantly for Na+,K(+)-ATPase and concomitant Mg(2+)-ATPase activity, but are the same in conditionally normal and cancerous tissues. This allows to detect correctly total levels of the Na+,K(+)-ATPase activity in the detergent-pretreated preparations. The moderate decrease of the Na+,K(+)-ATPase activity is revealed in carcinomas. It is concluded that a decrease of activity of the ouabain-sensitive human Na+,K(+)-ATPase is characteristic of colorectal carcinoma.     

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.     

Development of anhedonia under negative experience of social confrontations in male mice

Possible development of anhedonia in male mice under chronic stress produced by social confrontations was investigated. Cheese, instead of traditional sucrose solution, was used as a positive reinforcement. It has been shown that the controls, the winners with repeated experience of aggression accompanied by victories and the losers with repeated experience of social defeats, irrespective of their social status, preferred to eat cheese, but not pellets, under the free choice conditions--80% of total food. After three days of cheese deprivation, the least food motivation and the least level of cheese consumption were observed in the losers as compared with the controls and winners. Influence of social stress as well as negative psychoemotional state produced by social defeats, on development of anhedonia as a symptom of major depression, is discussed.