[Spatial imprinting influence on development of cognitive process in adult animals].

The influence of spatial imprinting on cognitive activity of adult mice F1 from DBA/2J C57BL/6J in a transformable multialternative maze has been studied. A control mice initially learned in a maze with "direct" and "bypass" pathway between feeders. They successfully formed a food-getting habit after 9-10 sessions using mainly direct pathway, so the final route decision was consistent with the principle of least action. Experimental mice previously placed into reduced maze with only "bypass" pathway between feeders for 1-2 trials (1-3 min), and turn up in the complete maze immediately after that. Experimental mice could not organize a food-getting behavior according a task conditions since attempted to include in final decision both "direct" and "bypass" pathways, united in a single ring-like construction. They demonstrated situational behavior running from one feeder to another one, despite of fact that therein had no feed. So it opposed the realization of least action principle, becoming a source of psycho-emotional stress. The results showed that spatial information perceiving in the first few minutes of exploring the experimental environment can manifest itself as the acquired preference and come in conflict with an instinctive one. Cognitive dissonance predetermined the direction of the cognitive process.

[Physiological effects induced by dermorphin synthetic analogue--opilong].

The effects of repeated opilong injections in a dose of 50 microg/kg/day on subsequent learning of Wistar rats have been studied. The substance caused significant anxiolytic and analgesic effects, as the majority of animals could be learned (90% against 40% in control group) despite of painful stimulus preceding to education. Opilong in a small dose displaced a relation of excitatory-inhibit processes to significant prevalence of excitation although the substance was already absent in an organism for a long time. Raised peripheral sensitivity in all rats, provoked by opilong, correlated with CNS hyper excitability, expressed in stressful, neurotic psychoemotional reactions and in the form of active avoidance. The biochemical blood analysis in opilong-induced rats demonstrated the attributes of prethrombosis in the form of fibrinolysis depression and hypercoagulation. A view is expressed, that the neuromediator brain systems can be the basic point of opilong action, that are responsible for the excitatory-inhibit conditions of CNS functioning referred on maintenance of conditioned field stability.

[Imprinting as a mechanism of information memorizing in the adult BALB/c mice].

Study of spatial learning in adult BALB/c mice revealed that a short exposition to the environment (from 3 to 8 minutes) could be enough for spatial information to be fixed in the long-term memory, and affected subsequent learning process in the new environment. Control group, learning in the same maze, followed the "shortest path" principle during formation of the optimal food-obtaining habit. Experimental animals, learning in a slightly changed environment, were unable to apply this rule due to persistent coupling of the new spatial information with the old memory traces which led to constant errors. The obtained effect was observed during the whole learning period and depended neither on frequency nor on interval of repetition during the initial information acquisition. The obtained data testify that memorizing in adult state share the properties with the imprinting process inherent in the early ontogeny. The memory fixation on all development stages seems to be based on a universal mechanism.

[Problem of controls in physiology and pharmacology: psychophysiological and morphofunctional effects of chronic saline administration].

The psychophysiological and morphofunctional effects of chronic administration of saline, which is commonly used as an active control, to Wistar rats were analyzed at different levels. The active control proved to be complicated by signs of stress manifested as increased corticosterone levels, changes in the homeostatic system, blood cytometric indices, morphofunctional states of the thymus and spleen, sharp suppression of the cognitive activity, and decrease in the motivational and locomotor activities. Pain expectation developed in animals after the second saline injection in the tail-flick test--pain sensitivity sharply increased in the session prior to the injection. These signs of stress should be taken into account for interpretation of the effects in drug tests.

[Individual sensitivity of Wistar rats to piracetam].

Effects of repeated piracetam (PIR) injections in a dose of 40 and 250 mg/kg/day on the learning in Water rats were studied. It has been found that character of the effects depends on typological features of the animals. Rats with strong predominance of excitation (choleric type) showed low sensitivity to PIR. Small dose of PIR provoked clear negative effect in rats with relative balance of the basic nervous processes: excitation and inhibition (sanguine and phlegmatic types). Despite of expressed activation of associative process, it complicated integrative activity. Small dose of PIR showed anxiolytic and psycho-stimulant actions only in initially unlearned rats characterized by high level of fear. Large dose of PIR had negative influence on the learning process in all animals, irrespective of typological features. Thus, the results of this study allow to suppose that the individual sensitivity of an animal to action of a pharmacological medication is caused by morpho-functional and neurochemical intraspecific heterogeneity.

[Quantitative urease test for Helicobacter pylori infection in patients with gastric and duodenal ulcer].

The monitoring for the presence of H. pylori carrier state in a group of patients with gastric and duodenal ulcer was carried out with subsequent determination of the relationship between the intensity of the urease activity of the bioptic specimen of the mucous membrane and the severity of the course of the disease. For this purpose we developed the scheme for the evaluation of the severity of the disease with quantitative criteria. The data obtained in this work showed no correlation between the severity of this disease and usease activity. Still the method of the quantitative determination of the urease activity of the bioptic specimen made it possible to evaluate the rate of the production of hydroxyl anions by a given H. pylori strain and thus quickly establish the presence of carrier state.

[Cytokines and cytokine therapy in gastrointestinal diseases]. / Tsitokiny i tsitokinoterapiia pri zabolevaniiakh organov pishchevareniia.

AIM: To compare cytokine status in gastrointestinal diseases (GID) with reference to etiological factor, course, stage, therapy of the disease. MATERIAL AND METHODS: Enzyme immunoassay was used to examine cytokines in the peripheral blood, tissue homogenates of 560 GID patients. GID were represented by ulcer disease (UD), cholelithiasis, chronic hepatitis (CH), glutenic enteropathy (GE), Crohn's disease (CD), nonspecific ulcer colitis (NUC). RESULTS: In chronic recurrent GID (UD, cholelithiasis, GE) early exacerbation was characterized by elevated concentrations of IL-1 beta, IL-6, IL-8. Concentrations of IL-12, Inf alpha, g, TNF alpha reached maximum on the height of the disease. Intensification of regenerative processes raised concentrations of IL-4, IL-10. An overall level of serum cytokines averaged 190-780 pg/ml, reaching in some patients with active disease 1200-3000 pg/ml, in remission 30-110 pg/ml, in the control 40 pg/ml. In chronic progressive GID the levels of IL-1 beta, IL-2, IL-8, IL-6 reached 30-80 pg/ml, IL-12, Inf gamma, TNF alpha--150-370 pg/ml. A rise in cytokines concentrations in inflammatory viral, bacterial, autoimmune GID was higher than in cancer, alcoholism-related diseases, metabolic disturbances. Basic therapy in patients with chronic recurrent GID led to a significant fall in concentration of serum cytokines. Therapy with monoclonal antibodies to TNF alpha was associated with transitory pronounced favourable changes in peripheral blood cytokine status. CONCLUSION: GID provoke elevation of serum and tissue cytokines, impairment of cytokine balance in correlation with the etiological factor, variants of the course, stage of the disease, on-going therapy.

[Psycho-emotional manifestations in rats with hippocampal lesions]. / Psikhoémotsional'nye proiavleniia u gippokampéktomirovannykh krys.

The study aimed at revealing psycho-emotional manifestations of Wistar rats in a problem situation when they had to solve a food-getting task in a multi-alternative maze. Bilateral lesion of dorsal hippocampus did not affect the learning process while the pattern of psycho-emotional manifestations changed in all the animals irrespective of their individual properties. The pverall effect was manifested in flatness of psycho-emotional responses as a result of reduction of extreme forms of both passive and active stress responses. Individual effects depended on the behavioural phenotype. Hippocampus lesion in initially excitable rats (10%) resulted in reduction of active stress responses (act/pass = 0.35/0.5 instead of 1.0/0.4 in control). Hippocampus lesion in initially inhibited rats (30%) did not affect the basic pattern of psycho-emotional responses, while in the rats with initially depressed cognitive activity (60%) it resulted in decreasing of passive and increasing of active stress responses (act/pass = 0.45/1/4 instead of 0.3/1.9). The findings suggest that hippocampus takes part in the psycho-emotional responses while the individual psycho-emotional pattern is determined by the morpho-functional features responsible for organisation of a psycho-emotional condition.

[Features of active control used in pharmacological studies]. / Osobennosti aktivnogo kontrolia, ispol'zuemogo v farmakologicheskikh issledovaniiakh.

The effects of 5 injections of salt solution and unfractionary heparin in dose 0.36 microgram/kg (Serva, Germany 10 kDa, activity 180 U/mg) have been studied in Wistar rats. It was found that two injections of salt solution were enough to form a stable defensive state in all rats which was manifested as an expectation of pain in tail-flick testing. The defensive motivation provoked by the injections negatively influenced the learning process as saline-induced rats refused to solve a food-getting task in a problem situation. Explorative and locomotor activities were depressed in these rats and were accompanied by numerous stressful and neurotic-like manifestations. Unlike saline-rats, practically all heparinized-rats instead of 45% of intact rats were able to solve a cognitive task despite the injections. Anxiety was decreased, but sensitivity to different external factors was increased in the heparin-induced rats. Formed habit in these rats was characterized by a high organization and stability. However, the majority heparin effects in tail-flick test were discovered when comparing the heparin-induced rats with intact ones and were not observed in comparison with the saline-rats. It is suggested that the saline-control should be considered as specific control having defensive features which are necessary to take into account in interpretation of effects of other pharmacological preparations.

[Retention of memory traces in rats subjected to 10-minute clinical death procedure]. / Sokhrannost' pamiatnykh sledov u krys, perenesshikh 10-minutnuiu klinicheskuiu smert'.

Retention of memory traces was tested on the 12th day after 10-min clinical death (CD) produced by the total cessation of blood circulation in Albino rats previously trained for operant food conditioning in a multiple alternative maze. It was found that the structure of memory trace (sequence of operant actions in the maze), motivation activity and habit organization after the resuscitation were completely preserved in all rats independently of the number of the memory traces formed. Short-term negative changes were revealed only in the character of habit realization: the efficiency and reproduction parameters such as "readiness", mobilization activity, and stability of habit realization had lower values during 2-3 sessions. The rate of their recovery after the CD depended on rat's initial motivation state: the higher was the initial motivation, the faster recovered all the reproduction parameters. It is suggested that the observed negative changes in habit realization were nonspecific and were provoked by the CD-induced hyperexcitability of rats.

[Psychostimulation of Wistar rats after intraperitoneal administration of high-molecular heparin]. / Psikhostimuliruiushchie éffekty vysokomolekuliarnogo geparina pri vnutribriushinnom vvedenii krysam linii Vistar.

The influence of repeated administration of heparin in learning was studied in Wistar rats (n = 20). High-molecular heparin (Serva, Germany, 10 kDa, activity of 180 IU/mg) was intraperitoneally injected daily in the dose of 64 IU/kg in a volume of 0.3 ml during 5 days prior to 4-link freechoice operant conditioning in a complex maze. As distinct from 40% of control rats, practically all heparin-treated rats were successful in conditioning. Parameters such as rate and efficiency of learning, behavior organization, habit stability, and extinction of errors were significantly better than in control animals. Anxiety was decreased, but sensitivity to external factors was increased in comparison with the control rats. The data obtained suggest that prior treatment with high-molecular heparin has a strong psychostimulant effect through activation of biogenic amines and formation of complexes with them.

[Magnetic field and alcohol addiction]. / Magnitnoe pole i alkogol'noe vlechenie.

The effect of weak disturbance (up to 300 microT) of natural magnetic field on the development of alcohol addiction in rats exposed to information load (training in a complex maze) was studied. It was found that learning against the background of inhomogenous magnetic field led to 3-13-fold increase of alcohol intake in 100% of rats. At the same time, under conditions of the same information load against the background of natural magnetic field, this phenomenon was observed in 45% of animals and was less expressed (a 2.4-fold increase). Unlike the control groups, the effect of magnetic field was independent neither on the level of initial alcohol preference, nor on the exploratory ability of animals. The increased alcohol uptake persisted for two months after the termination of the information load. It is suggested that the higher energetic level is needed in the presence of the weak inhomogenous magnetic field for normal exploratory activity. In this case, ethanol can serve as an additional source of energy.

[Response of sensorimotor cortex neurons to weak disturbances of the magnetic field in Wistar rats. Cytochemical study]. / Reaktsiia neironov sensomotornoi kory krys linii Wistar na slaboe vozmushchenie magnitnogo polia. Tsitokhimicheskoe issledovanie.

The influence of weak disturbances (up to 300 microT) of natural magnetic field on the protein metabolism in neurons of sensomotor cortex (layers III and V) in Wistar rats upon learning in a complex maze was studied. It was found that sensomotor neurons were very sensitive to weak disturbances of magnetic field. The protein content increased, while the nucleus-cytoplasm ratio and osmotic state of neurons remained unchanged. The specificity of neuron's reaction manifested itself in a sharp increase of nucleus and cytoplasm dimensions. In associative neurons (layer III), both the nucleus and cytoplasm were involved in the response; in efferent neurons (layer V), only nuclear parameters changed. The variance coefficients of all parameters of protein metabolism in sensomotor neurons, independently of their functional properties, were much higher than in control, which resulted in a wide diversity of cytochemical response.

[The acquisition of a cyclic maze habit in rats (as a model of cognitive activity) with removal of the amygdaloid body]. / Vyrabotka tsiklicheskogo navyka v labirinte u krys (kak model' kognitivnoi deiatel'nosti) pri udalenii mindalevidnogo kompleksa.

Learning cyclic habit in a multialternative maze (with a possibility of many rewarded choices) was shown to be possible for amygdalectomized rats. All three normal types of the "learning curves" (a number of cycles as a function of the number of sessions) were observed in rats after surgery, i.e., exponent, logistic function, and "no-trend" function. This is in agreement with Simonov's concept. However, the general style of behavior was changed. The behavior became "excessive": there was an increase in the number of errors and in the locomotion rate, which suggests a disbalance of emotional-cognitive interrelations. The extent of deviation from norm is different for each type. The findings suggest the different functional weight of amygdala in the normal activity.

[The neurochemical and behavioral indices of an acquired alcohol craving in rats under conditions of information loading]. / Neirokhimicheskie i povedencheskie pokazateli priobretennogo vlecheniia k alkogoliu u krys v usloviiakh informatsionnykh nagruzok.

The state of neurotransmitter systems was studied in the groups of Wistar rats discriminated by striving for alcohol and rejecting it after the information load (alimentary instrumental conditioning in a labyrinth). The specific activities of neurotransmitter metabolizing enzymes (MAO A and B, acetylcholinesterase, and acetylcholinetransferase) and the content of biogenic amines and their metabolites (serotonin, 5-hydroxyindoleacetic acid, noradrenaline, and dopamine) were measured in homogenates and subfractions of sensorimotor cortex and caudate nucleus. It was found out that the biochemical indices correlated with cognitive abilities of animals. Stress-resistant rats, which were capable for acquisition of the complex skill, refused alcohol after the information load and were characterized by activation of the brain neurotransmitter systems. The rats, which were unable to fulfill the cognitive task, began to abuse alcohol and were characterized by suppression of the neurotransmitter systems. It seems possible that the brain neurotransmitter metabolism adequately reflects the characteristics of the higher nervous activity of animals and their resistance to alcohol.

[The learning characteristics of rats under free-choice conditions]. / Osobennosti obuchenia krys v usloviiakh svobodnogo vybora.

The ability to organize a four-link operant food-procuring habit in a multiple alternative maze using the free-choice method was studied in albino rats. Three types of animals were observed which were different in the character of learning. The learning curve of 20% of rats had of exponential character (type I). Some animals (37%) acquired the skill through "insight" and the process of learning in these cases could be described by a logistic regression function (type II). The remaining rats (43%) refused from solving the intricate task and were able to acquire only the simplest form of a response, i.e., running to feeders. It is suggested that learning differences between the I and II types of animals may be associated with different strategies of problem solving: "procedural" (algorithmic) and "conceptual" (semantic).

[The cytochemical indices of the sensorimotor cortex neurons in rats differing in their trainability in a food-acquiring habit]. / Tsitokhimicheskie pokazateli neironov sensomotornoi kory krys, razlichaiushchikhsia po obuchaemosti pishchedobyvatel'nomu navyku.

Comparative study of protein metabolism in neurons of layers III and V of the sensorimotor cortex was carried out in two groups of Wistar rats, which differed in learning results: "bad" (60% of population) and "good" learners (40%). It was found out that the associative neurons (layer III) were most sensitive to cognitive load. In "bad" learners, an increase in nuclear and cytoplasmic dimensions and rise in protein concentration and content took place in these neurons, while in the efferent neurons (layer V) the protein content increased only in the cytoplasm. In "good" learners, the cognitive load led to a decrease in all the cytochemical parameters in neurons of the layer III while in the neurons of the layer V the content and concentration of proteins increased both in nuclei and cytoplasm. It is suggested that the character of protein metabolism changes produced by information load can be considered as a reflection of individual peculiarities of cognitive activity, and the extent of cytochemical changes as a reflection of complicity of a cognitive task.