[Participation of NO-synthase system in the stress-mediated reactions of the brain].

Neurosis-like status developing as a result of the exposure of animals to chronic stress, which is associated with a transitory cerebral hypoxia, could cause significant structural and functional alterations in many brain structures. Realization of humoral stress effects on the brain is mediated by both extra- and intracelullar signal molecules, among which nitric oxide (NO) is considered to be one of the most potent ones. Expression of neuronal constitutive (nNOS) and inducible (iNOS) isoforms of NO-synthase was studied by immunohistochemistry in the neurons of albino rat brain after exposure of animals to chronic stress resulting in the development of neurosis-like status. Chronic stress was shown to result in the increased expression of both nNOS and iNOS in many brain areas with the predominance in neocortex and hippocampus. The administration of nonspecific inhibitor of NOS, Nomega-nitro-1-arginine methyl ester hydrochloride (L-NAME) (10 mg/kg) resulted in the aggravated depression of the animals, associated with a decrease of locomotor and exploring activities that were evaluated using the traditional tests. The application of NOS activity inhibitor caused an insignificant rise only in iNOS expression. Thus the results obtained suggest that NO is involved in the realization of stress effects with the development of a neurosis-like status.

[Comparison of parameters of stress and trait anxiety in teenagers who are brought up in full, incomplete families, and families with the replaced parents].

166 teenagers in the age of 15-17 years were investigated on the influence of socially adverse conditions of education upon the level of trait anxiety and presence of stress. Teenagers who were brought up in socially unsuccessful conditions (in family with registered cases of alcoholism, violence, suicide, etc.; in family of relatives; with trustees) and also teenagers who were brought up in incomplete families show higher level of trait anxiety (even if initially they have low congenital parameters of neurotism) and more expressed stress both on psychological and physiological level in a greater degree than teenagers from family with mother and stepfather. Teenagers living in family with stepfather have parameters of anxiet similar to teenagers living in complete families.

[Blood testosterone in rats: correlation with individual anxiety and its derangement after the "death threat"].

After preliminary testing on a multiparameter scale, test and experimental groups of Wistar male rats were formed on the principle of identical distribution of individuals with different anxiety levels. A negative Spearman correlation between the testosterone blood concentration and the level of anxiety was observed in intact rats: the minimum hormonal concentrations (lower than 5 nmol/l) were found in rats with high anxiety, whereas the maximum concentrations (up to 16 nmol/l) corresponded to the higher anxiety level (prevalence of passive defense reactions during testing). After a sort-term exposure to life-threatening situation (viewing of a boa's attacking and devouring two victim rats from the test group), the correlation was deranged because of appearance of a scatter in testosterone blood concentration (from 3 to 21 nmol/l) in rats with low anxiety. Neurotization with inescapable pain stimulation also deranged the initial anxiety-testosterone correlation, but, as distinct from the exposure to life-threatening situation, eliminated individual differences in testosterone concentration at its low level. The results suggest the existence of multiple ways of adaptation to life-threatening situations in a rat population.

[A special case of learning disruption as a model of a disintegration phenomenon].

Combination of two factors in rats such as the isolation (during 2-4 months, beginning from the 21st day of age) and procedure of space cyclic learning results in a rare kind of behavioral strategy (in 30% animals), when the cyclic behavior is realized without food reinforcement. Such a dissociation between the vital motivation and searching behavior may be considered as an analogue of the disintegration phenomenon in neuropsychotic patients. The deep depression of learning owing to lowering of search represents the dominant type of behavioral disorders in isolants. The cyclic habit training, including a 2-months pause between two sessions, significantly increases behavioral search activity. The behaviors are accompanied by morphological shifts in the sensomotor cortex: significant decrease of the fifth layer (giant pyramids) thickness, selective lowering in the satellite glia density and elimination of normal behavior-glia correlations.

[The influence of chronic neurotization on the monoaminergic systems of various brain structures in rats with various typological characteristics].

Typological behavioral features of Wistar rats were tested in the open field and in Porsolt test. Rats were assigned to groups with high (HAct), medium (MAct), and low (LAct) behavioral activities. The same rats were assigned to high (HDep), medium (MDep) and low depressive (LDep) groups. The release of norepinephrine, dopamine, serotonin and their metabolites in homogenates obtained from the hypothalamus, hippocampus, frontal cortex and amygdala was assessed by microdialysis and HPLC. In these groups, the monoamine concentrations were different: the level of serotonin was higher in the hypothalamus and norepinephrine and 5-HIAA levels were lower in the hippocampus of MAct - MDep rats as compared to LAct - HDep. Chronic neurotization caused changes in monoamine concentrations in the hypothalamus and amygdala in rats of all groups, whereas in the hippocampus and frontal cortex monoamine changes were observed in HAct - LDep and LAct -HDep rats. The most prominent changes in monoamines levels in neurotized rats with different types of behavior were found in the frontal cortex, amygdala and hippocampus. The results show a correlation between the typological of behavioral characteristics and the reaction to stress of monoaminergic systems of the hypothalamus, hippocampus, frontal cortex and amygdala.

[Neuroses and their pathogenesis].

History and current state of the problem of experimental neuroses are reviewed in this article. The presented results of neurochemical, structural, and electroencephalographic investigations unravel earlier unknown aspects of the disease. Thus, circulatory cerebral hypoxia, as a principally new stage discovered for the first time in the development of an experimental neurosis allows the pathogenetically substantiated treatment with antioxidants to be applied in animal experiments and in clinical therapy of neurotic patients.

[Study of trait anxiety in children with different profiles of lateral organization after early social deprivation]. / Issledovanie lichnostnoi trevozhnosti u detei s razlichnym profilem lateral'noi organizatsii pri rannei sotsial'noi deprivatsii.

School behavior and learning were examined in 68 right-, lefthanded, and ambidextral 10-12-year-old children earlier exposed to social deprivation. Socially deprived children revealed stress and high trait anxiety. "Imposed lefthandedness" is considered to be an important factor responsible for the high level of trait anxiety. In the group of socially deprived children persons with sanguinic temperament showed the lowest, and melancholies showed the highest levels of trait anxiety as compared to the control group.

[Correction by succinic acid of behavioral and physiological parameters of neurosis-like condition in white rats]. / Korrektsiia povedencheskikh i fiziologicheskikh pokazatelei nevrozopodobnogo sostoianiia belykh krys vvedeniem iantarnoi kisloty.

The neurosis-like state of white rats is accompanied by development of cerebral hypoxia. Negative symptoms of the neurosis-like state (behavioral, anatomic and energy) were decreased by per os administration of succinate (30 mg/kg) during the second half of the neurotization process. Succinate provided chiefly the delayed action on the system arterial tension, on the succinate dehydrogenase and NADH dehydrogenase activity. The effects depended on the propensity of a rat to the catatonic "freezing". The "freezing" was detected by a specific breathing pattern: a short inhale and a long pause. In "freezing" rats succinate corrected the system tension to a greater extent, while in "non-freezing" animals it corrected to a greater extent the succinate and NADH dehydrogenase activities. The positive effect of succinate administration is probably associated with its antihypoxic properties.

[The correction of the manifestations of a neurosis-like state in white rats by using the vitamin complex Aekol]. / Korrektsiia proiavlenii nevrozopodobnogo sostoianiia belykh krys s pomoshch'iu vitaminnogo kompleksa aekol.

Behavior of neurotized white rats was studied in two experimental situations: during training for passive and active avoidance of electroshock applied to the limbs and during testing the acquisition of the conditioned avoidance. It was shown that in behavior of rats in the neurosis-like state the signs of anxiety and fear dominated, the orienting-exploratory behavior was suppressed. The state correction was performed by per os introduction of the natural vitamin complex Aekol during the neurotization of animals.

[A trial of the use of aekol in preventing psychoautonomic disorders]. / Opyt primeneniia aekola v profilaktike psikhovegetativnykh rasstroistv.

Autonomic dysfunction in chronic emotional stress is well documented. The aim of this study was to analyze the effects of natural antioxidant vitamin E (aekol). Twenty persons (16 women and 4 men, mean age 38 +/- 4 years) who reported recent occurrence of emotional stress were examined before and after a 4-week treatment with aekol (5 ml twice a day). Heart rate variability (taking into account very low-frequency (VLF, 0.003-0.04 Hz), low-frequency (LF, 0.04-0.15 Hz), and high-frequency (HF, 0.15-0.40 Hz) components) was computed from the power spectra (5-min epochs) of the EKG recorded in the patients in supine position. After the treatment, the HF power of the heart rate variability (an index of cardiac parasympathetic activity) increased (p < 0.05), whereas the VLF power (an index of the cerebral sympathetic activity) decreased (p < 0.01). The decrease in the VLF was accompanied by a reduction of anxiety level (p < 0.01). According to our hypothesis, the absolute and relative power of the VLF can be used as an index of anxiety or cerebral sympathetic activity, which significantly decreases after the aekol treatment.

[Effect of the short-term exposure to negative air ions on individuals with vegetative disorders]. / Vliianie kratkovremennogo vozdeistviia otritsatel'nymi aéroionami na organizm liudei s vegetativnymi narusheniiami.

The humans with vegetative disorder have been under the short-time exposition to negatively charged air ions, produced by Tchizhevski aeroionizer "Elion-132". The state of vegetative nervous system and some other physiological systems and organs of treated humans were estimated by acupuncture R. Voll method. It was found, that treatment by negatively charged air ions leads to the normalization of the state of mentioned above acupuncture points in the most (87%) of the tested humans with vegetative disorder. In 13% of tested persons these indicators became worse after this procedure. In the each case the changes in the state of different acupuncture points had the single-directed character. The suggestion was made, that vegetative nervous system plays the important role in the formation of organism's integrated reaction to the action of negatively charged air ions.

[Chronic stress increases the reactivity of central depressor mechanisms]. / Khronicheskii stress uvelichivaet reaktivnost' tsentral'nykh depressornykh mekhanizmov.

The activity of noradrenergic system of lateral hypothalamus and hemodynamics were studied during acute restraint in chronically stressed and control rats. Arterial blood pressure in rest was negatively proportional to basal norepinephrine concentration in dialysate of lateral hypothalamus. Animals with high increase of norepinephrine levels in dialysate during acute stress had rapid return of arterial blood pressure to basal values while stress-induced hypertension in the beginning of restraint was the same as in rats with low increase of norepinephrine levels. Data obtained show the depressor role of noradrenergic system of lateral hypothalamus. The enhanced reactivity of noradrenergic depressor system may be one of the mechanisms providing cardiovascular adaptation to stress.

[The activity of the monoaminergic systems of the rat hypothalamus in acute stress after chronic stressing]. / Aktivnost' monoaminergicheskikh sistem gipotalamusa krys pri ostrom stresse posle khronicheskogo stressirovaniia.

The influence of chronic stress (footshock combined with randomized light flashes) on acute stress-induced (immobilization) release of noradrenaline, dopamine and serotonin in rat lateral hypothalamus was assessed by microdialysis. The chronic stress resulted in an increase and prolongation of the acute stress-induced release of noradrenaline but not of dopamine and serotonin. The increased rate of accumulation of dioxyphenylacetic acid and unchanged accumulation of homovanillic acid (dopamine metabolites) and dopamine during and after the acute stress in chronically stressed animals reflect a rise of synthetic activity of catecholaminergic systems in response to acute stress and reuptake increase. Marked stress-induced increase in hydroxyindoleacetic acid in chronically stressed rats without any changes in the ST dynamics may be regarded in a similar way. A significant increase in potassium-stimulated release of all the studied monoamines was found while their basal level remained unchanged. The conclusions was made that the hyperergic release of neurotransmitters may be the basis of an inadequate response of animals to acute stress, i.e., one of the neurotic symptoms.

[The action of the neurotoxin AF64A on the reactions of neuroticized rats]. / Deistvie neirotoksina AF64A na reaktsii nevrotizirovannykh krys.

The effects of intracerebroventricular administration of ethylholine aziridinum ion (AF64A) were studied in neuroticized male Wistar rats. The cholinotoxin was bilaterally injected in the dose of 3 nmol. AF64A produced a significant decrease in arterial pressure and activity of respiratory enzymes succinate dehydrogenase and NADH-dehydrogenase in hippocampus and motor cortex. Increase in the local blood flow in the hippocampus and motor cortex had a compensatory character.

[The protective action of negative air ions in acute stress in rats with different typological behavioral characteristics]. / Zashchitnoe deistvie otritsatel'nykh aéroionov pri ostrom stresse u krys s raznymi tipologicheskimi osobennostiami povedeniia.

Exposure of rats during immobilization to negatively charged air ions prevented the development of pathological changes typical for acute stress. Such protective action of negative air ions was observed in all the experimental animals independently of their types of behavior.

[The behavioral characteristics of rats induced by partial degeneration of the hippocampal cholinergic neurons]. / Osobennosti povedeniia krys, vyzvannye chastichnoi degeneratsiei kholinergicheskikh neironov gippokampa.

The effects of intraventricular administration of ethylcholine aziridinium ion (AF64A) were studied in male Wistar rats. Bilateral injections of AF64A (3 nm/3 mcl) reduced the reactions to biological alarm signal and produced a decrease in the open-field activity 3 weeks after this lesion. The lesioned rats also displayed deficit in retention of a passive avoidance task.

[The participation of cerebral hypoxia in the pathogenesis of neuroses (a new concept)]. / Uchastie tserebral'noi gipoksii v patogeneze nevrozov (novaia kontseptsiia).

The data are presented concerning the state of vascular brain system during experimental neurosis in Wistar rats, the intricate cerebral hemodynamical disturbances, shifts in activity of the crucial enzymes of the mitochondrial respiratory chain, and activation of the lipid peroxidation processes. The positive results on treatment of the experimental and clinical neuroses with antioxidants which have antihypoxic properties are presented. Results on increase of resistance to stress in rats under the influence of negatively charged air ions with expressed antihypoxic are discussed. The general outline is given of the molecular neurochemical processes which accompany the development of neurotic diseases as well as of reversal of these processes due to the antioxidant therapy. The concept concerning the cerebral hypoxia in neuroses is based on the obtained evidence. This concept opens the principally novel pathogenetical approaches to treatment and prevention of these diseases.

[The prophylactic effect of negatively charged air ions in acute stress in rats with different typological behavioral characteristics]. / Profilakticheskoe vliianie otritsatel'no zariazhennykh aéroionov pri ostrom stresse u krys s raznymi tipologicheskimi osobennostiami povedeniia.

Typological characteristics of behaviour of 63 male white rats weighing 200-250 g were estimated by their locomotion in the open field. Acute stress was induced by putting the rats into narrow tubes for 1 h. Prior to the experiment, the rats were exposed to the air ions produced by Chizhevskii air ionizer ("Elion-132") for 2 h daily within a week. It was found out that the expression of separate pathological stress-induced changes depended on typological characteristics of rats. The air ions were shown to prevent completely the development of physiological changes caused by acute immobilization, including arterial pressure increase, gastric mucosa injuries (erosions, haemorrhage), changes in respiratory enzyme activity (succinate dehydrogenase and NADH-dehydrogenase) in brain cells, cardiac and adrenal mass increase in rats with the active type behaviour.

[The microcirculation and the succinate and NADH dehydrogenase activities of the brain in neurotic disorders of the higher nervous activity in white rats]. / Mikrotsirkuliatsiia i aktivnost' degidrogenaz SDG i NADH-DG mozga pri nevroticheskikh narusheniiakh vysshei nervnoi deiatel'nosti u belykh krys.

A correlation was made between microcirculation and energy metabolism in the brain of 50 neurotized rats. Neurotic disorders were defined by characteristics of conditioning, arterial pressure, breathing rate and heart rate. In vivo biomicroscopy revealed modification of the state of blood vessels at rest and inverted reaction of brain pial vessels of neurotized rats to bilateral occlusion of common carotid arteries. Ratio of activities of respiratory cycle enzymes (succinate and NADH-dehydrogenases) was indicative of hypoxic state of the animals under study.

[The normalizing effect of air ions on neuroticized rats with different typological behavioral characteristics]. / Normalizuiushchee vliianie aéroionov na nevrotizirovannykh krys s raznymi tipologicheskimi osobennostiami povedeniia.

The work was carried out in 98 white male rats weighting 200-250 g. Typological properties of behaviour were estimated by locomotor activity in the open field. Neurosis was induced by electro-pain irritation (15 min daily during 3 weeks), accompanied by the white noise (4 h daily). The rats were influenced by air ions generated by Chizhevsky air ionizer ("Elion-132") for 2 h daily during the period of neurotization. It was shown that the degree of some pathological changes in neurosis depended on typological properties of rats. Air ions were established to prevent completely development of physiological changes typical for the model of experimental neuroses, i.e., increase of arterial pressure, Hildebrandt index and gastric ulcer formation. Air ions significantly decreased the number of gastric mucous membrane erosions. Air ions normalized activity of respiratory enzymes (succinate dehydrogenase and NADH-dehydrogenase) in rat brain cells and activated their exploratory behaviour.