Main ethanol metabolizing alcohol dehydrogenases (ADH I and ADH IV): biochemical functions and the physiological manifestation.

The range of the biochemical reactions which can be catalyzed by ADH I and ADH IV is extremely wide. The most characterized functions of these enzymes are protection against excess endogenous acetaldehyde, products of lipid peroxidation, exogenous alcohols and some xenobiotics. It was found also that ADH I and ADH IV are important members of the enzyme system synthesizing retinoic acid (especially during embryogenesis). They can oxidize some steroids and participate in bioamine and prostaglandin metabolism but so far the extent of their contribution to the latter processes is under discussion. Recent data suggest a correlation between the activity of ADH I in some organs and fine physiological processes including behavior regulation and craving for alcohol in albino rats.

Alcohol dehydrogenase (ADH). Influence of homo- and heterologous ADH administration on albino rats craving for alcohol and on ADH isozyme activity in the liver.

The effects of homo- and heterologous alcohol dehydrogenase (ADH) administration into albino rats were investigated. It was found that homologous ADH increases and heterologous ADH decreases the craving for ethanol. The latter effect was accompanied by the appearance of anti-ADH-3 antibodies and by a decrease in ADH-3 activity in the liver. Craving for alcohol decreased after both active and passive immunization against ADH.

The effects of immunization against cholecystokinin fragment 30-33 in the behavior of white rats.

Active immunization of white rats with cholecystokinin-4 covalently linked to the antigen carrier BSA evoked long-lasting changes in the rats' behavior, which were in the opposite direction to the anxiogenic effects of cholecystokinin-4 itself, showing that immunization had anxiolytic effects. Immunoenzyme analysis demonstrated the presence of antibodies to cholecystokinin-4 in the serum of immunized rats. These data are interesting from the point of view of correcting pathological anxiety and fear states by inverse immunoregulation.

[Long-term correction of brain function. Prospects of immunologic approaches]. / Dlitel'naia korrektsiia funktsii mozga. Perspektivy immunologicheskikh podkhodov.

Among various approaches to long-term correction of the highest functions of the brain there are two methods that are particularly promising. These included: 1) induction of autoantibodies against the enzymes involved in the metabolism of neuroregulators by means of immunization of respective heterologous enzymes; 2) immunization by covalent conjugates of monomolecular neurotropic compounds and neuropeptides with antigen carriers. The investigations of both methods are reviewed and illustrated in experiments on albino rats during alcoholization and some other processes of pathological behavior formation. Evidence is provided for that behavior can be corrected for several months or longer.

[Induction of long-term depression (with anxiety and fear components) by immunization of rats against pargyline]. / Induktsiia dlitel'nogo sostoianiia depressii (s komponentami trevozhnosti i strakha) immunizatsiei krys k pargilinu.

The active immunization of albino rats against pargyline (a MAO B inhibitor) induced the formation of antibody to pargyline and results in deep depressive changes and fear. These changes were observed within 6 weeks after the first immunization. Therefore, it opens the possibility to model depression long by exerting the minimum influences. There was also a long-term modulation of craving for alcohol.

[The inverse immunoregulation of behavior and the problem of the existence of regulatory autoantibodies]. / Inversnaia immunoreguliatsiia povedeniia i problema sushchestvovaniia reguliatornykh autoantitel.

This paper analyzes the effects of active immunization against endogenic neuromediators, neuroregulators, enzymes (catecholamines, serotonin, various regulatory peptides, alcohol dehydrogenase) on a physiological status of the body. It is indicated that such an immunization results in a decreased level (activity) of some regulatory endogenic agents and accordingly to the long-term changes in physiological functions of the body including such complex as behavior of animals. The data given in this paper on the long-term experimental immunologic correction of such the forms of pathologic states as alcoholism, increased convulsive alertness, competitive behavior, phobias are indicative of both fundamental and applied aspects of using inverse immunoregulation method.

[Possible role of conformational changes in synaptic proteins in mechanisms of temporary connection formation]. / O vozmozhnoi roli konformatsionnykh izmenenii sinapticheskikh belkov v mekhanizmakh obrazovaniia vremennoi sviazi.

Possible mechanism and the role of structural changes in the proteins of synaptic membranes in the process of formation of the temporary connection is discussed on the basis of existing assumptions and experimental data. Our experimental data suggest that during learning the structural changes occur in the synaptic membrane which are due to the conformation changes in the external and the integral proteins of membranes. Low-molecular proteins of synaptoplasma may play the role of the "carriers" and connectors and at a certain stage promote a conformation changes in synaptic proteins.

[Effect of 8-Br-cAMP on the formation of conditioned reflex behavior in the white rat]. / Vliianie 8-Br-cAMP na formirovanie uslovnoreflektornogo povedeniia u belykh krys.

The influence of cAMP analogue 8-Br-cAMP on conditioning was studied in white rats. Two models of learning were used with different kinds of reinforcement, i. e. conditioned active avoidance and instrumental alimentary reactions in a complex maze. Intraventricular 8-Br-cAMP injection 4 or 24 hours before the beginning of learning improved the process of defensive as well as alimentary conditioning. Characteristics of formation of complex behaviour of experimental rats in a maze showed that under the influence of 8-Br-cAMP, not only conditioning was accelerated, but the process of optimal decision making itself was changed. The data obtained permit to suppose that 8-Br-cAMP first of all affects initially poorly learning rats.

[Proteins of rat brain synaptic structures during conditioned reflex activity]. / Issledovanie belkov sinapticheskikh struktur golovnogo mozga krys pri uslovnoreflektronoi deiatel'nosti.

A comparative study was made of the structural-functional groups of proteins of synaptic structures in the cerebral cortex of albino rats during elaboration of a simple food-procuring reflex in one session. The results of estimation of quantitative and qualitative protein changes by the methods of isotope analysis and discelectrophoresis on polyacrylamide gel point to dissimilar changes in membrane and synapto-plasmatic proteins during learning. The process of temporary connections formation is accompanied by structural-chemical reorganizations of the synaptic membranes which evidently involve conformative transitions of external and integral proteins. There is a drastic rise in the rate of metabolism in the group of watersoluble proteins during learning, along with a possibility of "local" changes of synthesis in the fraction of low-molecular proteins.

[Mechanisms of suppression of alcohol motivation after immunization of albino rats against alcohol dehydrogenase I: The role of ADH epitopes and ADH activity in the adrenal glands]. / O mekhanizmakh podavleniia alkogol'noi motivatsii pri immunizatsii belykh krys k alkogol'degidrogenaze I: rol' épitopov ADG i aktivnosti ADG v nadpochechnikakh.

Experimental results have demonstrated a significant decrease in the level of alcohol consumption by albino rats immunized with heterologous horse alcohol dehydrogenase. The role of ADH epitopes 9-14, 93-115, and 265-276 in this phenomenon was examined, and it was established that the latter sequence (265-276) plays the biggest role. The inhibition of ADH activity in the adrenals of immunized rats was much higher compared to the liver. We propose a hypothesis that the effect of alcohol dehydrogenase on alcohol consumption is connected with its role in catecholamine metabolism.

[Administration of the omega-3 polyunsaturated fatty acid drug eiferol decreases alcohol motivation in albino rats by elevating the level of antibodies to alcohol dehydrogenase]. / Vvedenie preparata polinenasyshchennykh zhirnykh kislot semeistva omega-3 (éiferola) snizhaet alkogol'nuiu motivatsiiu u belykh krys, povyshaia uroven' antitel k alkogol'degidrogenaze.

The study experimentally assessed the approach proposed by the authors to lower alcohol motivation, which involves enhancement of a specific immunity at the stage of alcoholization when acetaldehydemodified ethanol exchange enzymes [alcohol dehydrogenase (ADH)] and acetaldehyde dehydrogenase may be expected to occur. Omega-3 polyunsaturated fatty acid (PUFA) drugs enhance the formation of autoantibodies to modified ADH and decrease the activity of ADH in the stomach and liver. At the same time, PUFA drugs can, under certain conditions, produce an anti-alcoholic activity and a positive effect on the psychoemotional status of animals after the ethanol deprivation period.

[The action on brain functions in white rats of the immunostimulant Freund's complete adjuvant]. / Deistvie na nekotorye funktsii mozga belykh krys immunostimuliatora--polnogo ad''iuvanta Freinda.

The effect of immunostimulator--Freund's adjuvant complete on the nociception and learning of white rats using food-obtaining and avoidance of electric shock techniques has been studied. It has been shown that the adjuvant in doses for active immunization causes itself the expressed changes in animal behaviour. The adjuvant's injections significantly increases the learning ability of animals both with negative and positive reinforcement as compared with control one. The changes in pain severity is marked only for dose 0.2 ml. The nonspecific action of adjuvant should be taken into account in researches which use the active immunisation method.