[Structural-metabolic changes in neurons of hippocampus and neocortex under the influence of "polydan"].

The aim of this work was to study the influence of different regimens of polydan administration on the structural and metabolic state of neurons of rat hippocampus and neocortex. The animals of experimental groups were administered 75 mg/kg of polydan intraperitoneally once or 5 times. Animals of control groups received similar injections of sodium chloride isotonic solution. Light microscopic study of hippocampus and somatosensory area of neocortex demonstrated 4 types of neurons that could be distinguished according to the degree of their staining with methylene blue. Polydan administration resulted in redistribution of relative proportions of neurons of these types and in increase of the number of nucleoli in these cells, thus indicating an activation of synthetic processes. Quantitative ultrastructural analysis of ribosomes in the cytoplasm of neurons of hippocampal area CA3 and neocortical layer V has confirmed the activation of protein synthesis. Intensification of synthetic processes in neurons was further supported by the analysis of mitochondrial cristae and matrix. It is suggested that synthesis activation in brain neurons is a structural and functional basis for the mnemotropic effect of polydan.

Effect of polidan on ultrastructural changes in the cerebral cortex and hippocampus of rats.

Electron microscopy and morphometry of neurons in layer V of the somatosensory area in the neocortex and CA3 field in the dorsal hippocampus showed that single and 5-fold intraperitoneal injection of Polidan was followed by ultrastructural and metabolic changes in neurons reflecting activation of protein synthesis. The number of free ribosomes decreased; the number of polysomes and count of ribosomes in polysomes and tubules of the granular endoplasmic reticulum increased. Study of mitochondria and neuropil showed that Polidan activates synthetic processes in the neocortex and hippocampus. It should be emphasized that single treatment with Polidan led to functional activation of synthetic processes, while 5-fold injection of Polidan was followed by hyperactivation of synthetic processes and depletion of ultrastructures in the neocortex and hippocampus.

Morphofunctional changes in neurons of hippocampal fields and neocortical layers in rats treated with Polydan.

Light microscopy revealed four types of neurons differing by staining intensity and size in each of the pyramidal neuron populations in the dorsal hippocampal fields and layer V of the neocortical somatosensory area and in granular cells of the dentate fascia and stellate cells of layer II of the same cerebrocortical area in rats. Treatment with Polydan according to different protocols led to redistribution of these types of cells, which attests to stimulation of synthetic processes in these brain areas, rather than to similar sequence of the involvement of different brain areas in this process. Polydan promoted the increase in the mean number of nucleoli in the nuclei of neurons of all types, the degree of this increase being different for each type. It seems that morphological signs (staining intensity and number and size of nucleoli in the nuclei) reflect certain functional states of the neurons in the homogeneous populations. Presumably, various factors can stimulate transition of neurons from one morphofunctional status into another.

[Effect of polidan on the conditioned memory and structural and metabolic parameters of the rat brain neurons]. / Polidan--vliianie na uslovno-reflektornuiu pamiat' i strukturno-metabolicheskie pokazateli v neironakh mozga krys.

New experimental data on the mnemotropic (nootropic) properties of the well-known drug polidan (a DNA derivative) are summarized. The results obtained by histological techniques showed changes in the brain structure, indicating protein synthesis activation under the action of polidan. These results confirm prognostic function of the concept of evolutionary-molecular basis of memory.

[Effect of the novel dipeptide nootropic agent noopept and its metabolite cyclo-L-prolylglycine on the transcallosal evoked potential in the rat brain]. / Vliianie novogo dipeptidnogo nootropa noopepta i ego metabolita tsiklo-L-propilglitsina na transkallozal'nyi vyzvannyi potentsial mozga krys.

The effect of new nootropic dipeptides--noopept (N-phenylacetyl-L-prolylglycine, GVS-111) and its metabolite (cyclo-L-prolylglycine)--and a standard nootrope piracetam on the transcallosal evoked potential (TEP) in rat brain was studied. In the dose range from 150 to 300 mg/kg, piracetam increased the TEP amplitude, which exhibited a maximum after 1.5-2 h and then gradually decreased. Both noopept and cyclo-L-prolylglycine also increased the TEP amplitude, which attained a plateau and retained this level over the entire observation time (above 3.5 h). All the nootropes studied increased both components of the evoked potential. Piracetam and cyclo-L-prolylglycine led to an approximately equal increase in both waves, while noopept induced a somewhat greater increase in the negative TEP wave amplitude. It is suggested that the positive effect of noopept and cyclo-L-prolylglycine upon the interhemispheric signal transfer (indicated by the improved transcallosal response) can be considered as a potential neurophysiological basis for a positive drug influence on the behavioral level.

[Comparative analysis of memory pathologies of various genesis: epileptic patients and Chernobyl nuclear plant accident liquidators]. / Sravnitel'nyi analiz patologii pamiati raznogo geneza na primere liudei, bol'nykh épilepsiei, i likvidatorov avarii na ChAES.

Different types of short-term memory were examined in two groups of people: epileptic patients during remission and participants of cleaning after the incident at Chernobyl nuclear power plant. The control group matched the experimental groups by sex, age, and education. It was found that memory dysfunctions were similar independently of the kind of pathology. The associative memory was most vulnerable. This finding is explained in terms of the role of protein-nucleic synthesis (the molecular-universal aspect) in the formation of human and animal associative memory.

[Positive effect of pyavit on formation and retention of the passive avoidance conditioned reaction in rats]. / Uluchshenie vyrabotki i vosproizvedeniia uslovnogo refleksa passivnogo izbeganiia u krys pod vliianiem piiavita.

In the paper are presented the results of the study of Pyavit, a complex leech preparation from, whose effects on the memory may be dependent on DNA methylation (one of the mechanisms of gene expression regulation). A positive effect of Pyavit on formation and retention of passive avoidance conditioned reaction was demonstrated in rat experiments.

[Effect of piracetam on the conditional reflex memory under probable reinforcement conditions]. / Vliianie piratsetama na uslovnoreflektornuiu pamiat' krys v usloviiakh veroiatnostnogo podkrepleniia.

The effect of piracetam on the development of a two-link system of feed-procuring conditioned reflexes was studied in rats with probability reinforcement. The experiments showed that piracetam improves both the current learning process and the memory track (previous experience) reproduction. In addition, the drug decreases the role of the probabilic character of reinforcement, thus facilitating the synthesis of two reflexes in a united functional complex.

[The nootropic and anxiolytic properties of different doses of piracetam]. / Nootropnye i anksioloiticheskie svoistva raznykh doz piratsetama.

The effect of piracetam at various doses on the behavioral and electrophysiological characteristics was studied, including the development of passive and active avoidance conditional reflexes in rats, their behavior in conflict situations, and the transcallosal evoked response (TER) in rabbit brain. In the dose range from 50 to 300 mg/kg, piracetam improved the avoidance performance of both types and produced a dose-dependent increase in the TER amplitude, but did not affect the behavior of rats in conflict situations. As the drug dose was increased to 400-1000 mg/kg, the positive learning influence disappeared (sometimes the effect was even negative) and the TER increase changed to decrease. In contrast, the conflict situation tests revealed pronounced anxiolytic activity of piracetam at elevated doses. Thus, the nootropic and anxiolytic effects of piracetam (and, probably, of the other tranquilizers as well) do not coexist and are significantly shifted relative to one another on the dose scale, being probably realized via different mechanisms.

[Positive effect of DNA derivative polidan on acquisition and reproduction of the passive conditioned avoidance reflex]. / Uluchshenie vyrabotki i vosproizvedeniia uslovnogo refleksa passivnogo izbeganiia pod deistviem derivata DNK (polidan).

Effect of DNA derivative of biological origin on rat memory was studied. The positive influence of the drug on formation of memory trace and retention was shown. The results are discussed in the frames of the hypothesis of the common molecular mechanisms underlying memory optimization by different psychotropic drugs.

[The effect of bemitil on conditioned-reflex memory in normal rats and under stress exposures]. / Vliianie bemitila na uslovnoreflektornuiu pamiat' krys v norme i pri stressornykh vozdeistviiakh.

The authors studied the effect of the actoprotector bemitil on the conditional-reflex memory of rats and its functional disorder by disturbance of the cause-effect (abatement of the avoidance reaction) or space relations. Intraperitoneal injections of 1.8 mg/kg of bemitil were given daily 30 min before the experiment. The training of animals improved authentically from experiment to experiment. Thus, the drug, possesses the nootropic properties. Exposure to stressogenic factors of various depth demonstrated the stress-protective effect of bemitil.

[The effect of the new nootropic dipeptide GVS-111 in different functional disorders of the escape reaction]. / Effekt novogo nootropnogo dipeptida GVS-111 pri razlichnykh funktsional'nykh narusheniiakh reaktsii izbeganiia.

The authors studied the effect of a new nootropic agent with anxiolytic properties GVS-111 (ethyl ether N-phenylacetyl-L-prolylglycine) on formation of the avoidance reaction (AR) in rats and its functional disorders which were induced by two methods. In one case the stereotype of the relations between the stimulus, reaction and its consequence which developed during the experiment were urgently disturbed: the change of the animal to the other half of the chamber in response to a conditioned stimulus did not lead to its cutting off and prevention of the electropain stimulation for three successive combinations (AR error). In another case the spatial stereotype of the experiment was altered by changing the place of the opening through which the animal avoided the stimulus (spatial remodeling). Intraperitoneal injection of GVS-111 (0.1 mg/kg/day) improved the learning, but the effect differed from experiment to experiment. Along with this, the dipeptide prevented AR disturbance during the error and quickened restoration of the habit in spatial remodeling. It was shown earlier that AR disorders during an error are prevented by anxiolytics and nootropic agents but during spatial remodeling only by nootropic agents. It may be assumed that the positive effect of GSV-111 on AR in functional disorders is due to its nootropic effect.

[The effect of piracetam on the behavior of Nauphoeta cinerea cockroaches in an open field]. / Vliianie piratsetama na povedenie tarakanov Nauphoeta cinerea v otkrytom pole.

For 30 min the behaviour of 164 male cockroaches was studied in an "open field" analog. At the 31st min the electrical light was switched on and the examination was continued for 10 min. It was found out that the insects placed in the "open field" and subjected to a sudden illumination behaved in a similar way. After the initial freezing a sharp increase in the motor activity was observed with subsequent habituation. Per os administration of 200-400 mg/kg of piracetam (a solution of 5 mg of the drug and 500 mg of honey in 5 ml of water) did not change the freezing period but accelerated habituation and decreased the locomotion augmentation caused by the light. The obtained data suggest that piracetam improves memory and non-associative learning and exerts a stress-protective effect on cockroaches.

[Differences in the effects of piracetam and fenazepam in emotional stress caused by the spatial reversal of a habit]. / Razlichie v éffektakh piratsetama i fenazepama pri émotsional'nom napriazhenii, vyzyvaemom prostranstvennoi peredelkoi navyka.

Emotional stress was caused in rats by changing the location of the gate in the shuttle chamber through which training had been accomplished in the previous experiments. The procedure led to disorder of the avoidance response (AR) and increase of intertrial responses (ITR). Phenazepam (0.1 mg/kg) prevented increase in the number of ITS. Piracetam (300 mg/kg) reduced the sharp growth of ISR but, in contrast to phenazepam, it provided a higher level of AR reproduction. The ISR were greater in piracetam than in phenazepam administration. The obtained results show that the suggested model allows the difference in the effects of piracetam and phenazepam to be disclosed.

[A reversible functional disorder of the escape reaction as a model for studying the effect of tranquilizers]. / Obratimoe funktsional'noe narushenie reaktsii izbeganiia kak model' dlia izucheniia vliianiia trankvilizatorov.

A model of reversible functional disorders of the escape response (ER) for studying the effect of tranquilizers is proposed. The model is based on the unexpected action of electric current used regardless of the specific relation (stimulus-response effect). This results in enhanced emotional stress, reduces ER, and increases intersignal responses. The model proposed has less in common with the conflict situation because no interference of the opposite motivations is suggested, namely, the formation and disturbance of ER is based on the same unconditioned stimulus and test performance does not suggest punishment with electric current. We found that hydazepam (20 mg/kg) prevents and phenazepam (0.1 mg/kg) reduces the ER disorders.

[A comparative analysis of the effect of nootropic preparations with different chemical structures on the failure of the escape reaction in rats]. / Sravnitel'nyi analiz vliianiia nootropnykh preparatov razlichnoi khimicheskoi struktury na sboi reaktsii izbeganiia u krys.

The nootropic agents pyroglutamyl-D-alanine amide (TGS-20), mechlofenoxate, and mexidole versus piracetam were tested for their effects on the reversible impairments of cognitive brain functions, on the demolition of active avoidance responses in rats. TGS-20 (1 mg/kg/day) and mexidole (10 mg/kg/day) injected intraperitoneally 30 minutes prior to the experiment showed a normalizing effect in smaller doses than did piracetam (300 mg/kg/day). Mechlofenoxate (50 mg/kg/day) displayed a lower protective effect.

[A general biological hypothesis on the mechanisms of the effect of different psychotropic agents that optimize memory]. / Obshchebiologicheskaia gipoteza mekhanizmov vliianiia razlichnykh psikhotropnykh sredstv, optimiziruiushchikh pamiat'.

Possibility of interpretation of the effects of psychotropic drugs on memory is considered from the viewpoint of general biological conception on molecular mechanisms of memory. Previous studies of functional-molecular mechanisms of memory in animals at different evolutionary levels, carried out by the author and collaborates, became a theoretical basis of the hypothesis proposed. In particular, genome modification was established to be induced by learning and specific and universal components of memory were revealed. Possibility of genome activation in the brain is considered as one of deciding factors in the mechanism of memory optimization by psychotropic drugs.