[Effects of inmecarb on alcohol intake and the state of hepatic cytochrome P-450 system during various stages of experimental alcoholism in rats]. / Vliianie inmekarba na potreblenie alkogolia i na sostoianie sistemy tsitokhroma P-450 pecheni na raznykh stadiiakh éksperimental'nogo alkogolizma u krys.

The influence of the new anti-alcohol drug Inmecarb on the alcohol consumption as well as on activity of the liver cytochrome P-450 system was studied in rats during chronic alcohol intoxication in the free choice situation between water and 15% ethanol solution. It was shown that voluntary alcohol consumption of different duration (10 days to 8 months) does not change the activity of liver cytochrome P-450 system. Inmecarb treatment (40 mg/kg, i.p. twice a day) during 14 days resulted in decrease of alcohol consumption in rats. This effect was most pronounced in late stages of experimental alcoholism. Inmecarb decreases the cytochrome P-450 content and suppresses the activity of aniline hydroxylase in rats with different duration of voluntary alcohol intoxication, but most pronounced effect was observed during the late stages of experimental alcoholism.

[A decrease in the acute toxicity of ethanol produced by zinc sulfate]. / Snizhenie ostroi toksichnosti étanola sul'fatom tsinka.

It was shown that zinc sulphate injection during the acute alcohol intoxication resulted in the decrease of anaesthetic and toxic effects of ethanol. The most effective dose was 15 mkg/kg i.p. The possible mechanisms are discussed.

[Prevention of the formation of alcoholic motivation in rats using zinc sulfate]. / Preduprezhdenie vozniknoveniia alkogol'noi motivatsii u krys sulfatom tsinka.

The experiments carried out on albino male rats have shown a decreased zinc content in the brain of active animals selected under conditions of forced swimming test, as compared to passive animals. 10-day intraperitoneal injection of biotic zinc sulfate dose (50 micrograms/kg) resulted in the prevention of alcohol motivation in active animals. There was no such effect in passive animals. The differences between basic mechanisms of alcohol motivation in different groups of animals are suggested.

[Participation of GABA in mediating the effects of ethanol in rats with differing susceptibility to the development of experimental alcoholism]. / Uchastie GAMK v oposredovanii éffektov etanola u krys s razlichnoi predraspolozhennost'iu k razvitiiu éksperimental'nogo alkogolizma.

The influence of ethanol and of GABA receptors blocker bicuculline on recovery cycles of primary response of the sensorimotor cortex was studied in rats with strong and weak inclination to development of experimental alcoholism. It is found that in rats of the first group, inhibition in the cerebral cortex was weakened in comparison with the rats of the second group. Ethanol in non-narcotic doses intensified the inhibitory processes and its effects could be prevented or suppressed by bicuculline. The conclusion is made about GABA participation in mediation of ethanol effects on inhibitory processes in the cerebral cortex.

[Liver cytochrome P-450 system in rats with a varying susceptibility to the development of experimental alcoholism]. / Sostoianie sistemy tsitokhroma P-450 pecheni u krys s raznoi predraspolozhennost'iu k razvitiu éksperimental'nogo alkogolizma.

The cytochrome P-450-dependent monooxygenase system of the liver was studied in laboratory noninbred male rats selected according to the intensity of their initial alcohol motivation and the dynamics of these parameters was followed up during 10-day alcoholisation. It was shown that in the animals inclined to the development of alcoholism the activity of the monooxygenase system (cytochrome P-450, B5; enzymes: aminopyrine N-demethylase, aniline p-hydroxylase, NADPH-cytochrome c-reductase) is higher than in the animals noninclined to the development of this disease. 10-day alcohol consumption in the free-choice situation between water and 15% ethanol solution did not change the parameters investigated. The only exception was NADPH-cytochrome c-reductase: its activity grew in both the groups of the animals by 40-75%.

[Effect of septal damage on alcoholic motivation in the rat]. / Vliianie povrezhdeniia peregorodki na alkogol'nuiu motivatsiiu u krys.

Interconnection between predisposition to depressive-like state (DS) in stress situation and heightened addiction to ethanol was studied in nonlinear male white rats. Electrolytic lesion of the septum in animals inclined to the development of DS, led to a change from the passive type of reaction in stress conditions to the active type. The rate of formation of alcoholic motivation in these animals decreased in comparison with sham-operated rats. The effect of the septal lesion in rats with formed addiction to alcohol was less expressed. Conclusion is made that the passive type of reaction in extreme conditions is significant for the formation of alcohol motivation in rats, especially at early stages.

[Pharmacokinetics of ethanol in the blood of rats in various stages of chronic alcoholism]. / Farmakokinetika étanola v krovi krys na raznykh stadiiakh khronicheskoi alkogolizatsii.

Kinetics of ethanol content, as a criterion of tolerance to the substance, was studied in rat blood at various steps of experimental alcoholism by means of gas-liquid chromatographic analysis. Initial addiction to alcohol was associated with its increased metabolism in the animals. Activation of ethanol-oxidizing enzymatic systems was observed in chronic alcoholization under conditions of free choice. This activation became statistically distinct after 10 days of the contact with alcohol. The activation of ethanol metabolism was maintained within 4 months and decreased after 8 months of alcoholization.

[Concentration of endogenous ethanol and alcoholic motivation]. / Uroven' éndogennogo étanola i alkogol'naia motivatsiia.

Trials with patients suffering from stage II chronic alcoholism and normal test subjects as well as experiments made on male C57BL mice (with genetically determined alcoholic motivation) and CBA mice (with genetically determined alcoholic aversion) and random-bred male rats with different levels of initial alcoholic motivation have shown the presence of reverse proportional dependence between blood plasma endogenous ethanol and alcoholic motivation.

[Various features of the emotional behavior of animals with pronounced alcoholic motivation]. / Nekotorye osobennosti émotsional'nogo povedeniia zhivotnykh s vyrazhennoi alkogol'noi motivatsiei.

Testing of animals with different degrees of manifestation of attraction to ethanol showed that in conditions of zoosocial conflict rats--potential dipsomaniacs have less competition abilities in their struggle for the aims of biological value as compared to the rats, who are not dipsomaniacs. Their failure in a conflict situation leads to the fact, that while getting in the same or some other stress conditions for the second time, the animal fully gives up activity and makes no attempts to overcome these situations. This weak behavioural activity of such rats is based on a great tendency to the development of depressive-like state. Alcohol in certain doses (0.5 g/kg) normalizes the behaviour of rats--potential dipsomaniacs. This, probably, explains the appearance of alcoholic motivation in these animals.

[Formation of experimental alcoholism in a population of crossbred rats]. / Osobennosti formirovaniia éksperimental'nogo alkogolizma v populiatsii besporodnykh belykh krys.

Experiments on random-bred rats were made to study the relationship between the duration of ethanol anesthesia and the time course of alcohol consumption for 8 months. Short-sleeping rats with ethanol anesthesia lasting less than 90 minutes exhibited initially high and steady alcoholic motivation. Meanwhile long-sleeping rats with ethanol anesthesia lasting over 175 minutes demonstrated high level of alcoholic motivation only under stressful conditions. After 8 months of keeping in isolated cages long-sleeping rats demonstrated the same intensity and steadiness of alcoholic motivation as was the case in short-sleeping animals. Long-sleeping rats differed from short-sleeping ones in hypersensitivity to the toxic action of ethanol. It is inferred that in random-bred rats, there are at least two forms of experimental alcoholism.

[Toxicological characteristics of an experimental model of alcoholism in rats]. / Toksikologicheskaia kharakteristika éksperimental'noi modeli alkogolizma u krys.

The morphological appearance and morphometric indicators (the content of RNA, protein, glycogen and fat) of the internal organs of random-bred male rats were studied 10 days, 6 and 12 months after voluntary consumption of 15% ethanol. Alcohol consumption for 12 months provoked marked pathological alterations of the animals' internal organs, similar to organ pathology in alcoholic patients. The time course of these changes was marked by stages which correlated with the stages of experimental alcoholism formation, classified according to the behavioral criteria. The conclusion is made about adequacy of the model in question for screening and study of the pharmacological agents fit for the treatment of alcoholism.

[Characteristics of the formation of an ethanol preference in rats of both sexes]. / Osobennosti formirovaniia predpochteniia étanola u krys raznogo pola.

A high level of initial alcoholic motivation in females is associated with a high metabolic rate as regards ethanol and a low one as regards acetaldehyde in the estrus. The diestrus period is little characteristic in this respect. A high level of alcoholic motivation in males is associated with a high metabolic rate of ethanol and a low one of acetaldehyde. The risk of ethanol preference to water formation is 1.5-2 times higher in male rats than in female ones.

[Tyrosine hydroxylase activity in the brains of rats with different levels of initial alcoholic motivation]. / Tirozingidroksilaznaia aktivnost' v mozge krys s razlichnymi urovniami iznachal'noi alkogol'noi motivatsii.

Activity and KM of hypothalamic tyrosine hydroxylase (TH) were studied in rats preliminarily tested for predisposition to high ethanol consumption. It was shown that as regards cofactor of DMPH4 enzymatic reaction, KM of hypothalamic TH of animals with an initially high alcoholic motivation is lower than that from the brain of animals rejecting alcohol, being 0.34 +/- 0.3 mM and 0.46+/- 0.10 mM, respectively. A conclusion is made that the catecholaminergic system is involved into the realization of the rewarding effects of ethanol.

[Ethanol elimination in rats with different levels of alcoholic motivation]. / Eliminatsiia étanola u belykh krys s razkichnym urovnem alkogol'noi motivatsiia.

It has been established during intraperitoneal and oral administration of ethanol to white rats in a test dose of 1 g/kg that in the animals with high alcoholism motivation, the rate of alcohol elimination from blood is fairly high, while the species with low alcoholic motivation are marked by a slower ethanol elimination. In rats with high alcohol motivation, the time of ethanol anesthesia significantly exceeds that in the animals with low alcoholic motivation. The blood levels of ethanol at the moment of wake up are identical in both groups. A conclusion is made about the relationship between the elimination pattern, activity of alcohol-metabolizing enzymatic systems and predisposition to alcoholism.

[Individual features of emotional reactivity of animals as a prerequisite for the development of attraction to alcohol]. / Individual'nye osobennosti émotsional'noi reaktivnosti zhivotnykh kak predposylka vozniknoveniia vlecheniia k alkogoliu.

The experiments showed that alcoholic attraction in some rats and its absence in others are due to different reactions of their central nervous system to alcohol. A clear interconnection is found between the absence of alcoholic attraction, the appearance of aggressiveness during the administration of alcohol in situations of common escape and its inefficiency as to the activation of the structures of the positive reinforcement. It is also shown that in rats with alcoholic attaction this drug causes a tranquilizing effect and activates the structures of the positive reinforcement. The methods are described which help to reveal the attraction to alcohol in rats in one-time administration of its small doses.

[Effect of pharmacologic substances on the dominance-submission relationship in a pair of rats]. / Vliianie farmakologicheskikh veshchestv na otnosheniia dominirovaniia i podchineniia v pare krys.

The effect of neuroleptics (chlorpromazine, trifluoperazine, haloperidol), antidepressants (amitryptyline, imipramine), tranquilizers (diazepam, chlordiazepoxide, benactyzine) and stimulant d-amphetamine on the domination and subordination relations formed as a result of competitive behaviour in a pair of rats was studied. The drugs in question proved to violate the set relations of domination and subordination weakening the attacking ability of dominating rats and strengthening the defensability of the subordinate ones. With increase of antidepressants dosage received by a subordinate rat its competing ability becomes enhanced too; this may cause a change in domination.

[Effect of pharmacologic substances on the avoidance reflex in a group experiment on rats]. / Vliianie farmakologicheskikh veshchestv na refleks izbeganiia v gruppovom éksperimente krys.

It has been established that the avoidance reflex is disturbed in rats when performed in the presence of a group of non-learned rats. The degree of the disturbance depends on the number of non-learned animals present and the extent if their emotional excitation. Tranquilizers: diazepam, chlordiazepoxide and benactyzine; neuroleptics: chlorpromazine, trifluoperazine and galoperidol; antidepressants: amitriptilin and imipramine in certain doses, while improving the avoidance reflex in the presence of a group of excited rats, do not affect the disturbance of avoidance in the presence of a group of calm rats. It has been assumed that these drugs prevent the appearance of emotional excitation in learned animals in response to that in the non-learned animals surrounding them.