Immobilization stress-induced thymocyte apoptosis in rats.

Immobilization of rats is a well known model of emotional stress. We studied apoptosis in rat thymocytes during immobilization for 2-8 hours (h). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells increased with time of immobilization. The positive cells increased significantly after 2 h and comprised about 33% of total cells after 8 h. The apoptotic cells aggregated as scattered foci predominantly in the cortex of the thymus and diffusely distributed with time of the stress. The DNA laddering also increased with time of immobilization, which was inhibited by a glucocorticoid receptor antagonist, RU-486. These results suggest that the emotional stress evoked by immobilization induces thymocyte apoptosis through glucocorticoid overflow.     

Relationship between the sequelae of zoosocial isolation and individual characteristics of the animal

The changes were studied of various psychophysiological characteristics of mice behaviour, arising after prolonged solitary isolation in cages. The qualitative specificity of such changes is non-uniform and depends on the animals' individual characteristics (spontaneously aggressive or nonaggressive after isolation). Two types of the consequences of isolation are singled out: 1) General changes (non-specific) arising in all groups of mice; 2) Special changes (specific), typical of a certain group of animals only. In the group of aggressive mice there is a difference between aggression enhanced by isolation, and that which developed in the course of isolation. The most substantial qualitative changes in behaviour takes place in the latter case. It has been suggested that only individual approach makes it possible to determine exactly the qualitative aspects of social isolation consequences.     

Role of free radicals in stress-induced neurobehavioural changes in rats

Effect of restraint stress (RS) and its modulation by antioxidants were evaluated on elevated plus maze (EPM) and open field (OF) tests in rats. Restraint stress (RS for 1 hr) reduced the number of open arm entries, as also the time spent on open arms indicating enhanced anxiogenic response in the EPM test as compared to normal non RS group of rats. Pretreatment with ascorbic acid (100 and 200 mg/kg) and alpha-tocopherol (30 and 60 mg/kg) attenuated these RS-induced effects. In the OF test, RS-reduced (a) ambulations; and (b) rearings, whereas an increase was seen in (a) latency of entry and (b) number of fecal boluses. The RS-induced changes in OF parameters were reversed after pretreatment with the antioxidants, (ascorbic acid and alpha tocopherol). Biochemical data showed that RS enhanced MDA levels in both serum and brain, and these were attenuated after pretreatment with the antioxidants. The pharmacological and biochemical results indicate that free radicals might be involved in such stress-induced neurobehavioural effects.     

Effect of beta-endorphin on catecholamine levels in the rat hypothalamus and cerebral cortex

The present paper deals with the effect of beta-endorphin on catecholamine content in the hypothalamus and cerebral cortex of male rats. beta-endorphin was found to decrease catecholamine content in the rat brain, with the degree of reduction depending on the brain topography and the time following the peptide administration. 5 min later no changes in catecholamine content were observed either in the hypothalamus or in the cerebral cortex. 20 min later beta-endorphin induced a statistically significant fall of catecholamine concentration in the hypothalamus. A tendency towards its decrease was also observed in the cerebral cortex. 60 min later beta-endorphin produced an insignificant decrease in catecholamine level in both brain areas under study. It may be therefore suggested that beta-endorphin-induced decrease of catecholamine content in the hypothalamus and cerebral cortex represents one of the mechanisms underlying beta-endorphin stimulating action on a number of trophic functions of the hypophysis.     

Immobilization stress-induced antioxidant defense changes in rat plasma: Effect of treatment with reduced glutathione

• 1.1. We examined immobilization stress-induced antioxidant defense changes in rat plasma and observed the antioxidant effect of reduced glutathione (GSH) administration on these changes.
• 2.2. Immobilization stress induced severe bleeding in the stomach and a significant increase in plasma levels of thiobarbituric acid receives substances (TBARS).
• 3.3. Immobilization stress induced a significant decrease in plasma iron-binding, ironoxidizing protections and radical scavenging activity.
• 4.4. Plasma levels of ascorbic acid, ascorbyl radical and superoxide dismutase activity remained unchanged following immobilization stress.
• 5.5. Treatment with GSH showed a significant protective effect on stomach bleeding, on the increase in plasma TEARS, and on the decrease of iron-binding, iron-oxidizing protection and radical scavenging activity in plasma.
• 6.6. These results suggest that immobilization stress induces generation of reactive oxygen species and decreases the endogenous antioxidant defenses, which can be attenuated by extracellular administration of antioxidant GSH.

     

Neuronal activity of the sensorimotor area of the rabbit cerebral cortex in zoosocial behavior

The present study was aimed to investigate the neural activity during competitor relationships in the social interactions and operant feeding behaviour. In experiments on three pairs of rabbits the activity of 32 sensory-motor cortex neurones were analyzed. 21 neurones were found specialized relatively to different acts of social behaviour. They did not participate in provision for "individual" types of behaviour.     

The characteristics of the change in the catecholamine content of the brain in inbred mouse strains under zoosocial stress]

Noradrenaline (NA) and dopamine (DA) contents in various brain regions and their dependence on genotype, determining predisposition to domination, were studied during 7 days after the formation of artificial micropopulations consisting of 6 male mice of different genotypes. Significant changes of NA level were found in the olfactory bulbs and in the medulla oblongata and of DA in the hypothalamus and the hippocampus. Genotypic differences in NA levels were found in the hypothalamus and in DA levels--in the hippocampus. Reactions of RT males predisposed to domination differed both in noradrenaline and DA systems of the brain from the reactions of the males genetically predisposed to subordinate type of behaviour. Interconnection between the amines content both inside and between catecholamine systems was revealed.     

Influence of muscular exercise on blood catecholamine levels in rats]

Lactacidemia, catecholaminemia and blood pressure have been measured in normal rats submitted to a swimming exercise. They are overloaded (6% body weight). Lactacidemia is increased after 15 minutes swimming. Adrenalinemia and noradrenalinemia are also statisticaly increased. Blood pressure falls during the exercice period. Hypotension is prevented by beta adrenergic blockade.     

Characteristics of the intraspecies interaction of rats with differing zoosocial experience

It has been found that among white outbred rats with different experience of intraspecies contact four types of reaction to the partner are singled out in the "stranger-resident" test: active, neutral passive, highly-aggressive. Belonging to one or another type is determined by the level and correlation of aggression and intraspecies sociability. Among animals isolated in an adult age, all four types of reaction to the partner are represented while in rats kept in isolation since 13--14th day of life only one type is presented--the active one. For animals of the control group the first three types of reaction are typical. It is revealed that only "late" isolation leads to a pathological increase of aggressivity in a part of the animals; an increase of aggression in "early" isolants may be considered as a consequence of sharp rise of intraspecies sociability. Conclusion is made about principal difference in mechanisms of aggression increase in "early" and "late" isolants.     

Time-related changes in size of nuclei of pinealocytes in rats

Summary In a study of 96 adult male Sprague-Dawley rats, da-and time-related changes of the mean nuclear volume of pinealocytes were determined with the aim of testing the reproducibility of the karyometric findings described by Quay and Renzoni (1966). It is shown (i) that statistically significant differences exist between the central and peripheral mean volumes of pinealocyte nuclei/group of animals and time point (p<0.001), (ii) that the day and time related differences are statistically different in both regions (p<0.001), (iii) that in the center and periphery of the pineal body different diurnal patterns exist, and (iv) that the diurnal patterns are not parallel in the two regions.The question discussed is (i) whether or not probable superimposed infradian rhythms may account for the different diurnal patterns, and (ii) whether these patterns in the two regions indicate functional differences between the cortex and the medulla of the rat pineal body.Supported by the Deutsche Forschungsgemeinschaft (Grant Vo 135/4) within the Schwerpunkt-programm NeuroendokrinologieThis paper is an abridged version of a thesis submitted for obtaining the degree of Dr. med., Fachbereich Medizin, University of Mainz     

Glucose tolerance, insulin and catecholamine levels in germfree rats.

Glucose was administered intravenously to 50- and 100-day-old GF and CV rats. Fasting blood glucose levels in GF and CV rats were found to be comparable. Glucose tolerance tests showed that GF and CV rats clear glucose from the blood at a similar rate. Although insulin concentrations in 100-day-old GF rats tended to be somewhat lower than in CV rats, the percentage increase during the 30-min period after glucose administration was similar, and matched the increase in blood glucose. Levels of plasma catecholamines were analyzed fluorometrically and were found to be comparable in 100-day-old GF and CV rats. It was concluded that insulin insufficiency plays no role in the syndrome of metabolic anomalies demonstrated by the germfree rat.     

Stress-inducing behavioral changes and the functions of the neurohormonal systems in monkeys of different social ranks]

As a result of intensive stressful stimuli hamadryas baboons developed, depending on their hierarchic status, depression-like states varying in severity. Their development correlated with a drastic release of biogenic amines, activation of pituitary-adrenal system and inhibition of hormonal function of the gonads. It is shown that dominant and low-rank monkeys, in spite of the differences in their initial psychoemotional states and in the blood levels of mediators and hormones, demonstrated marked disintegration in their individual and social behavior. There was a larger increase in the blood concentrations of dopamine, serotonin and cortisol and more significant inhibition of testosterone production under the influence of two-hour immobilization as compared to the subdominant animals.     

The effect of compound nutrients on stress-induced changes in serum IL-2, IL-6 and TNF-alpha levels in rats

The effect of compound nutrients on serum concentrations of the cytokines, such as interleukin (IL)-2, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in immobilization and cold water-immersion stressed rat were investigated. Oral (gavage) administration of compound nutrients was found to attenuate the acute and chronic immobilization and cold water-immersion stress-induced increase in serum IL-6 level and decrease in IL-2 level. Compound nutrients exerted different effects on TNF-alpha level in two different models studied, with reduced serum TNF-alpha level in acute stress, while no significant effect in chronic stress. These results suggested that compound nutrients might be proposed as a possible candidate in the research or therapeutic modulation of stress-related disorders.     

Molecular changes in inbred mice with individual vulnerability vs resilience to stress-induced depressive-like state

The C57BL/6 mice were subjected to a chronic combined stress which resulted in the induction of a depressive-like state. The occurrence of a depressive-like state was defined by a decrease in sensitivity to the reward determined by the diminished preference of sweetened solutions over regular drinking water. Such decrease is generally considered as a sign of an unhedonic-like state: one of the key features of clinical depression. Applied here, the paradigm in mice allows unhedonia induction in a subpopulation of stressed animals (54% in the current study); remaining mice are regarded as resilient to stress-induced hedonic deficit. The resilient subgroup is taken, therefore, as a "functional control" for those effects of stress that are not accompanied by development of the stress-induced depressive-like state in mice. The analysis of the mRNA extracted from the hippocampi of stress-subjected and home-cage control mice enabled the assessment of gene expression level of over 13 000 genes. This study showed that unhedonic mice are characterized by an up-regulation of 278 and down-regulation of 174 genes related mostly to the CNS development and functions, inter-cellular interactions and signalling, neurological disorders, apoptosis and behavioural regulation. Resilient animals demonstrated up-regulation of 924 and down-regulation of only 29 genes that control formation of cell assemblies, molecular transport, CNS functioning, neurological disorders and various biochemical reactions. Thus, gene expression profiles in the hippocampus of susceptible vs resilient to stress-induced unhedonia inbred subgroups of animals are strictly distinct in both quantity and quality.     

Effect of interferon-alpha on tyrosine hydroxylase and catecholamine levels in the brain of rats

We investigated the effect of interferon on tyrosine hydroxylase (TH) and catecholamine levels in the brains of 12-week-old male Wistar rats. Interferon-alpha (300,000 IU/kg/day, s.c.) was administered to rats for 7 days. Locomotor activity of interferon-alpha-treated rats was significantly lower than that of control rats. Norepinephrine and dopamine levels and TH activities in the cerebral cortex, hypothalamus and medulla oblongata of interferon-alpha-treated rats were significantly higher than those of control rats. Norepinephrine and dopamine levels and TH activities in the thalamus and hippocampus were not different between interferon-alpha treated and control rats. These results suggest that interferon-alpha-induced depression may be related to change in the catecholamine synthetic pathway in the central nervous system.     

Effect of berberine on catecholamine levels in rats with experimental cardiac hypertrophy

The aim of this study is to investigate the effect of berberine on catecholamine level (adrenaline and noradrenaline) in rats with experimental cardiac hypertrophy. Cardiac hypertrophy(CH) was induced by suprarenal abdominal aorta constriction, and the drugs were administered for 8 weeks starting from 4 weeks after surgery. The degree of cardiac hypertrophy was determined by heart and left ventricular weight. The level of adrenaline(AD) and noradrenaline(NA) was detected by HPLC. The data showed that in the CH model rats, the level of plasma and left ventricular tissue AD, and the level of NA in plasma were higher than that of the age-matched controls(indicating increased "total" sympathetic activity). The level of NA in left ventricular tissue of CH model rats was however lower than the age-matched controls. Berberine and captopril showed significant effect on inhibiting the development of cardiac hypertrophy. Berberine decreased plasma NA level and the AD level both in plasma and left ventricular tissue, but had no effect on improving the cardiac NA depletion. Captopril showed significant effect on increasing the depleted cardiac NA and in reducing the elevated plasma NA level. These findings show the efficacy of berberine on modulating the sympathetic nervous activity of rats with experimental cardiac hypertrophy, and reflect the therapeutic potentials of berberine in patients with cardiac hypertrophy and chronic heart failure.     

Immobilization stress-induced lesions of structures of the midbrain reticular formation

Emotional stress in rats resulted in blood-brain barrier increased permeability and brain parenchymal vessel disruptions. Stress induced microvascular damages were mainly observed in midbrain reticular formation. In this article the components of midbrain reticular formation were studied 1, 2, 4 and 6 weeks after immobilization stress. The destructive changes in some neurons, glia cells and myelin fibers were shown up to 6 weeks after immobilization. The signs of the recovery were also observed. It was supposed that the brain parenchymal vessel damages under emotional stress were due to the stress induced locus coeruleus dysfunctions.