[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 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.

Effect of eiconol enriched with omega-3 polyunsaturated fatty acids on rat behavior and alcohol motivation.

We evaluated the effect of eiconol containing polyunsaturated fatty acids on the behavior and alcohol motivation in rats. Administration of eiconol for 10 days to alcoholized rats against the background of ethanol deprivation produced a sustained suppression of alcohol motivation and corrected deprivation-specific behavior.

[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.

[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.

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.

[Effect of immunization to cholecystokinin fragment (30-33) on the behavior of albino rats]. / Vliianie immunizatsii k fragmentu kholetsistokinina (30-33) na povedenie belykh krys.

Active immunisation of albino rats by the BSA-conjugated CCK-4 induced formation of antibodies to the CCK-4 and some long-term changes of the rat behaviour. These changes were contrary to anxiogenic effect of the CCK-4 and demonstrated an anxiolytic effect of the immunisation. The data obtained suggest a possibility of an immunocorrection of pathological anxiety and fear by an inverse immunoregulation.

GABA-induced changes of the tissue-specific peptide pool of white rat brain.

Internasal administration of gamma-aminobutyric acid (GABA) induced prolonged behaviour changes and the appearance of three new compounds absent in the brain extracts of control rats. Two peptides associated with GABA administration were isolated and sequenced: Thr-Tyr-Thr-Phe, which corresponds to a gamma-immunoglobulin segment, and Val-Leu, which is present in a great number of proteins, hence its precursor could not be established. The third compound was not amenable to the Edman degradation technique. The data obtained show that the introduction of a neurotransmitter could cause specific changes in the levels of tissue-specific peptide components.

Pargyline conjugate-induced long-term activation of monoamine oxidase as an immunological model for depression.

We describe an animal model of long-term depression based on active immunization of albino rats against BSA-conjugated inhibitor of monoamine oxidase, antidepressant, pargyline. Immunization resulted in anti-pargyline antibody formation and significant activation of monoamine oxidase A in brain. Immunized rats demonstrated potent decrease of motor, orientation and exploratory activity, increase of the immobility time ("despair") in Porsolt test, as well as notable signs of fear and anxiety in elevated plus maze. The cognitive processes were not significantly affected: the speed of learning with negative and positive reinforcement was not diminished. Complex effect on craving for alcohol (long-term suppression after short-term increase) was also demonstrated. The long-term (more than 45 days) depression achieved in this model makes it potentially important tool for testing new antidepressant pharmaceuticals.

[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.

[Anxiety-inducing and -inhibiting agents: differential effect of pentagastrins on the white rat behavior]. / Induktory i ingibitory trevozhnosti: differentsial'noe deistvie pentagastrinov na povedenie belykh krys.

Parenteral administration of des-BOC-Pentagastrin induced the anxiety and fear manifestations, depressing also explorative behaviour in open field experiments in rats. Intranasal administration evoked similar effects, whereas pentagastrin reduced the anxiety level, increasing explorative behaviour. Pentagastrin and des-BOC-Pentagastrin displayed antagonism at the receptor level.

[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.

Influence of the immunization against heterologous alcohol dehydrogenase on liver alcohol dehydrogenase isozymes and alcohol abuse of rats.

The possible biochemical and immunological mechanisms of the previously discovered phenomenon of significant and prolonged decrease of alcohol abuse of albino rats after the intravenous injection of the heterologous alcohol dehydrogenase (ADH) were studied. It was found that immunization of rats against horse liver S-ADH result in the appearance of a high titre of antibodies against rat liver ADH-3 isozyme. This isozyme is responsible for the metabolism of 90% of alcohol administrated in vivo. It is shown that immunization against horse liver S-ADH leads also to a significant (2--3-fold) lowering of the activity level of ADH-3 in rat liver. The activity level of the other rat ADH isozymes, ADH-1 and ADH-2, was not found to be changed. The intravenous injection of the specific anti-(horse liver S-ADH) serum, purified by affinity chromatography on immobilized horse liver S-ADH, resulted in a significant decrease of alcohol abuse in alcohol-dependent animals. These results allow us to assume an important role of rat liver ADH-3 in the mechanism of alcohol addiction.

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 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.

[The convulsive activity of white rats after immunization with a conjugate of sidnofen and serum albumin]. / Sudorozhnaia aktivnost' belykh krys posle immunizatsii kon''iugatom sidnofena s serumal'buminom.

The influence of white rats immunization by a covalent conjugate of serum albumin with sydnophen on the seizure activity in the single and repeated injections of pentylenetetrazole was investigated. The immunization lowered the seizure activity in single injections of threshold doses, (60 mg/kg) of pentylenetetrazole. The repeated daily injections of the drug in subthreshold doses (30 mg/kg) inhibited the process of "kindling" effects formation.

[Active immunization to exogenous and endogenous antidepressants. The formation of antibodies to biogenic amines and peptide regulators]. / Aktivnaia immunizatsiia k ékzogennym i éndogennym antodepressantam. Obrazovanie antitel k biogennym aminam i peptidnym reguliatoram.

The active immunization of rabbits and white rats to antidepressant sydnophen results in the formation of antibodies binding norepinephrine, dophamine, serotonine as well peptide regulatory compounds: substance P, pynorphine, vasopressin and beta-endorphin. The immunization against endogenic antidepressant thyroliberin induces the formation of antibodies to the same biogenic amines and to the gamma-aminobutyric acid, oxytocin and leu encephalin. The data obtained are discussed in connection with some physiological and biochemical changes found earlier during immunization to antidepressants.