[The harmful action of ethanol on the liver: the role of alcohol dehydrogenase and aldehyde dehydrogenase]. / Povrezhdaiushchee deistvie étanola na pechen': rol' alkogol'degidrogenazy i al'degiddegidrogenazy.

White rats were divided into water-preferring (WP) and ethanol-preferring (EP) groups, on the basis of their preferable drink: either water or 15% solution of ethanol. Each of these groups was then subdivided into groups which were given to drink for 1 year 15% solution of ethanol (ethanol-treated) or water (controls). Alcohol dehydrogenase/aldehyde dehydrogenase activity ratios (ADH/AlDH) in livers of WP controls were considerably higher than those in EP controls. The difference in ADH/AlDH has somewhat decreased after ethanol treatment. However, this ratio remained the highest in the WP alcohol-treated group. The signs of proteinic and lipid dystrophy of the liver in alcohol-treated WP rats were expressed much more clearly than in all other groups. It is concluded that in the liver of animals with a high ADH/AlDH ratio there are favourable conditions for accumulation of a toxic hepatocyte-damaging acetaldehyde.

[Current aspects of the search of effective nootropic drugs]. / Sovremennye aspekty poiska éffektivnykh nootropnykh sredstv.

The authors review different mechanisms of mnemotropic and cerebroprotective effects of nootropic drugs. The data concerning the molecular mechanisms of action of the structural analogs of the memory stimulant ethylnorantifeine (etimizol) have been summarized and analyzed. It is shown that the effects of antifeines on the retention of the conditioned reflexes are independent of their effects on the cAMP system and structural-functional condition of the neuronal membrane. The key role in the action of these compounds on the long-term memory is played by the activity of the genetic apparatus. The existence of nootropic receptors in neuronal chromatin is assumed.

[Changes in the bioelectrical activity and temperature of paired brain formations in the rabbit in a single ethanol administration]. / Izmenenie bioélektricheskoi aktivnosti i temperatury nekotorykh parnykh obrazovanii golovnogo mozga krolika pri odnokratnom vvedenii étanola.

In chronic experiments on rabbits, in initial period of single action of ethanol, reduction was observed of the dominating frequency of the theta-rhythm and synchroneity of summated bioelectrical activity of homotopic zones and suppression of EEG manifestation but preservation of parameters of the interhemispheric zeta-wave and of temperature asymmetry in the dorsal hippocampus in response to electro-cutaneous stimulation. Late period of ethanol action was characterized by lowering of the amplitude of superslow activity, its inversion in symmetrical areas of the visual neocortex and instability of other parameters.

[The effect of etimizol on the excitability and spontaneous super-slow activity of the structures of the rabbit brain]. / Vliianie étimizola na vozbudimost' i spontannuiu sverklmedlennuiu aktivnost' struktur mozga krolika

Spontaneous superslow electrical brain activity and its changes were studied in acute experiments on curarized rabbits after administration of etimysol in doses of 1.0, 1.5 and 2.5 mg/kg. The effect of the drug persisted for three hours. Two oscillation phases were recorded in the medial group of mesencephalic reticular nuclei and the lateral nucleus of the hypothalamus: a short positive phase and a prolonged negative one. In other brain structures only negative waves were recorded. A significant functional rearrangement of correlative connections of brain structures took place in 90 minutes after the drug administration. The factor analysis showed that the most subtle connections were preserved in the neocortex and the dorsal hippocampus.

[Characteristics of the super-slow electrical activity of the brain when exposed to the action of neurotropic substances altering short-term memory]. / Kharakteristika sverkhmedlennoi élektricheskoi aktivnosti mozga pri deistvii neirotropnykh veshchestv, meniaiushchikh kratkosrochnuiu pamiat'

Superslow electrical activity was studied after the action of neurotropic drugs on curarized rabbits with gold electrodes implanted in the deep brain structures. Intramuscular administration of 1/5 mg/kg dose of ethimizol, of 5 mg/kg of ethipyrol, or of 1/5 mg/kg of metamizyl led to a reciprocity of the oscillation amplitudes between the field CA-3 of the dorsal hippocampus and the medial nuclear groups of the reticular formation. Ethimizol and ethipyrol, though producing a similar final effect, act differently on the duration and phases of slow oscillations. Micropolarization of the dorsal hippocampus field CA-3 with a 2.5 microampere current lengthened the action of the neurotropic drugs, up to six hours in the case of ethimyzol. A mathematical vector analysis has shown that the angle of the wave amplitude vector in space depends both on the characteristics of the neurotropic drug and the excitability level of field CA-3 of the dorsl hippo-campus. A slow electrical potential reflecting the capacity of the electric field of a brain structure is likely to be one the major components controlling the conformation position of the receptor proteins.

[The participation of RNA synthesis in the process of the acquisition and retention of conditioned reflexes (a study using antifeins)]. / Uchastie sinteza RNK v protsesse vyrabotki i sokhraneniia uslovnykh refleksov (issledovanie s ispol'zovaniem antifeinov).

RNA-synthesizing activity of neuronal nuclei in the neocortex of rats increases after the termination of conditioning depending on the degree of learning. RNA synthesis shifts induced by propylnorantifein and the demethylated derivatives of ethylnorantifein are correlated only with the influence of the drugs on the retention but not the learning. Participation of RNA synthesis by the neurons of the neocortex in the mechanisms of long-term memory is discussed.

[One of the methods of treatment of affective disorders in patients with alcoholism]. / Ob odnom iz metodov lecheniia affektivnykh narushenii u bol'nykh alkogolizmom.

It has been demonstrated by a double blind placebo-controlled study that transcranial electric treatment (TET) by means of combination of direct current and pulse current and pulse current at a frequency of 70-80 Hz is an effective method of correcting affective disorders (anxiety, depressions) in patients suffering from alcoholism. The therapeutic effects of TET are coupled with changes in GABA and monoamine metabolism rather than in beta-endorphin as well as with a decrease of the latent period of the occurrence of alpha-rhythm after eyes closing.

[S. V. Anichkov--man and scientist (on the centenary of his birth)]. / S. V. Anichkov--chelovek i uchenyi (k 100-letiiu so dnia rozhdeniia).

The paper is devoted to a brief review of the research and public activities of Professor Sergei V. Anichkov; the prominent Soviet pharmacologist. He was Hero of Socialist Labour, V. I. Lenin and State Prize winners and Academician of the USSR Academy of Medical Sciences. It also summaries the main biographic data on the scientist and his theoretical and practical achievements in various areas of pharmacology. Great emphasis is laid on S. V. Anichkov's scientific school and his work in the Department of Pharmacology (he was head of the Department from 1948 to 1981), Institute for Experimental Medicine, USSR Academy of Medical Sciences.

[The pharmacology of memory (results and prospects)]. / Farmakologiia pamiati (nekotorye itogi i perspektivy).

Principal possibilities and limits of using the pharmacological approach for control of memory in studies of neurophysiological and neurochemical mechanisms of learning and memory in humans and animals are reviewed as well as its place in experimental and clinical therapy of memory disorders. Using an unspecific connector aethimizol as a pharmacological probe aided to assess changes accompanying the formation and consolidation of memory traces. The significance of fast and slow bioelectrical brain activity in the memory processing, the role of enzymes involved in transcription and template chromatine activity of the neurons under the effect of drugs on memory and learning, the correlation between time-depending learning and the pattern of RNA synthesis in brain cells, as well as possibilities and pathways of utilization of drugs in the correction of the long-term memory matrix formed by a stable pathological state of the brain, are discussed.

[Correlation of the minute waves of superslow activity and hippocampal temperature in altered function of the central nervous system]. / Sootnoshenie minutnykh voln sverkhmedlennoi aktivnosti i temperatury gippokampa pri izmenenii funktsional'nogo sostoianiia tsentral'noio nervnoi sistemy.

One-minute oscillations of the infraslow activity were recorded within the range of 0 to 1 Hz with indwelled electrodes in the rabbit hippocampus. The oscillations disappeared for 5-hour period after L-DOPA administration. The phenomenon could be prevented with ethimisol. A correlation was found between the amplitude of the infraslow oscillations and the temperature of the dorsal hippocampus in different states of the c. n. s. induced by catecholaminergic serotoninergic and cholinergic neurotropic substances.

[Interhemispheric relation of brain structures in various functional states of the central nervous system]. / Mezhpolusharnye vzaimootnosheniia struktur mozga pri raznykh funktsional'nykh sostoianiiakh tsentral'noi nervnoi sistemy.

In rabbits with indwelled gold electrodes, multiminute oscillations of infraslow activity were recorded within the range from 0 to 1 Hz. The temperature of cerebral structures was recorded from symmetrical areas with the aid of thermocouple. Changes of the functional state were induced by means of 1) unilateral microstimulation of frontal neocortex with 1.5-2.5 microA; 2) administration of neurotropic activators: aethimizole and its analogue: and 3) prolonged administration of ethanole. All these influences sharply increased the natural functional interhemisphere assymmetry inducting a rearrangement of intracentral interrelationships. Use of the neurotropic activators (aethimizole and IEM-476) temporarily restored the normal interaction between the cerebral hemispheres even if the functional interhemisphere asymmetry was still obvious.

[Dynamics of 1-minute superslow oscillations during the process of formation of a shortened reflex]. / Dinamika minutnykh sverkhmedlennykh kolebanii v protsesse formirovaniia ukorochennogo refleksa.

Formation of encephalogenic shortened reflex in rabbits induced specific local changes of amplitudes of the 1-min waves. Etimizol rapidly stabilized the level of the 1-min waves and fixed the reflex, keeping the local character of the response. Propylnorantiphein enhanced corticofugal projections to the thalamus. The shifts in the brain energy exchange (the creatin--phosphate, glycogen contents) coincided in time with the amplitude shifts of the 1-min waves and occurred within 20--30 min after administration of neurotropic drugs lasting 2--3 hrs. The etimizol recruited both alpha-and beta-adrenoreceptors whereas the propylnorantiphein involved mainly the alpha-adrenoreceptors. Etimizol, being an unspecific connector, enhanced consolidation of the shortened reflex increasing the local response to electric stimulation, whereas propylnorantiphein aided to spreading of the responses over to the thalamic nuclei.

[Relationship between the minute superslow oscillations and the level of energy supply in brain tissue]. / Zavisimost' minutnykh sverkhmedlennykh kolebanii ot urovnia énergeticheskogo obmena tkani golovnogo mozga.

In animals, an increase in glycolysis intensity and processes of oxidative phosphorylation in the brain correlated with the steady potential shifts within the range of 0--1.0 Hz in the neocortex, dorsal hippocampus, and thalamic nuclei. The neurotropic drug ethymizol revealed two effects depending on the initial functional state of the rabbit: 2.5 mg/kg of the drug enhanced the amplitude of the minute waves in the frontal neocortex and dorsal hippocampus, increasing the metabolic rate in the unsteady period of conditioning, whereas after the fast conditioning the drug rendered background values to the minute oscillations and elongated the extinction of conditioned reflexes. The ethymizol appears to be an unspecific connector.

[Neuropharmacology yesterday, today and tomorrow]. / Neirofarmakologiia vchera, segodnia i zavtra.

Three main directions of neuropharmacology developing at the S. V. Anichkov Department of Pharmacology of the Institute of Experimental Medicine, include the pharmacology of neurogenic damages of visceral organs, the pharmacology of memory disorders and the psychoneuropharmacology. The evolution of the outlook and the main achievements are described. The perspectives are analysed.

[Alcohol dehydrogenase in the blood of healthy people and in patients with chronic alcoholism]. / Alkogol'degidrogenaza syvorotki krovi zdorovykh liudei i bol'nykh khronicheskim alkogolizmom.

Activity of alcohol dehydrogenase (ADH) was estimated using highly sensitive spectrophotometric procedure with p-nitrose dimethylaniline as a substrate in blood serum of control healthy persons without a history of alcohol abuse and of the patients with chronic alcoholism. The ADH activity in the control group was about 0.55 +/- 0.04 microM/min/L and in the patients it was 2.5-5-fold higher. A direct correlation was found between the ADH activity and duration of alcohol abuse. In the patients with alcohol abstention syndrome the activity of ADH was 4.2-fold higher as compared with controls. During the remission, from 2 months up to 5 years, the enzymatic activity decreased, but was still distinctly higher than the control values.