[The "phenomenon of ethanol preference"]. / O "fenomene predpochteniia étanola".

The problem of using the "phenomenon of ethanol preference" under conditions of a free choice between ethanol and water as a behavioural model of alcoholism is discussed. The methodical aspects of the model are considered: the regimen of the animals' keeping, the criteria of preference, the concentrations of ethanol solutions, the schedule of presentation of the solutions. There was shown the principal similarity between the changes in the behaviour and biological parameters of the animals preferring ethanol and the changes observed in the man suffering from chronic alcoholism. It is concluded that despite the imperfection of the model the "phenomenon of ethanol preference" remains fairly valuable for studying the etiopathogenesis of alcoholism and developing the methods of the therapeutic action on the patient.

[Possibilities for behavior correction in a learned ethanol preference in female and male white rats]. / Vozmozhnosti korrektsii povedeniia pri sformirovannom predpochtenii étanola u samok i samtsov belykh krys.

Correction of behavior of rats preferring for a long time ethanol but not water may be performed using the agents enhancing sexual activity of animals of both sexes: apomorphine (1 mg/kg), bromocriptine (1 mg/kg) and yohimbine (4 mg/kg). Normalization of behavior of the rats manifested by not only a decrease of total ethanol consumption but also by a change of alcohol preference. Bromocriptine exerted the predominant effect on females, and yohimbine on males. Apomorphine was effective in the animals of both sexes but its efficacy was higher in females. The agents produce opposite changes depending on the animal sex in ethanol level during the withdrawal period, the rate of ethanol elimination in the blood at its administration in a test dose and the reaction of self-stimulation of the lateral hypothalamus. Female rats proved to be more sensitive to the drugs' effects related to changes in ethanol metabolism rate. Male animals were more responsive to the effects due to changes in the positive reinforcement system.

[Effect of bromocriptine in experimental alcoholism in rats of both sexes]. / Deistvie bromkriptina pri eksperimental'nom alkogolizme u krys raznogo pola.

It has been shown in experiments on intact rats that bromocriptin (1 mg/kg) produces opposite changes on the self-stimulation of the lateral hypothalamus: facilitates it in females and inhibits in males, whereas administered in a dose of 10 mg/kg inhibits it in animals of both sexes. It has been established in experiments on rats preferring ethanol to water that the drug in a dose of 1 mg/kg reduces the degree of ethanol preference only in females while the dose of ethanol consumption declines in animals of both sexes. Besides, bromocriptin decreases the rate of ethanol elimination from blood (3-fold in females, and 1.8-fold in males) and does not interfere with the reduction of ethanol concentration characteristic for the time of withdrawal.

[Self-stimulation characteristics and endogenous ethanol in rats of different sexes]. / Osobennosti samostimuliatsii i éndogennyi étanol u krys raznogo pola.

It has been shown in experiments on rats that in females, the threshold of self-stimulation of the lateral hypothalamus was 1.5-2 times higher than in males. Besides, the rate of self-stimulation with subthreshold currents was 57% higher in the estrus than in the diestrus. Measurement of the blood level of endogenous ethanol and animals' mass on daily self-stimulation for 8-10 weeks permitted making correlations with analogous parameters in rats of both sexes preferring ethanol to water for a long time. In both cases, the levels of endogenous ethanol, which were higher in females than in males, were lower than in intact animals. In addition, there was an increase in the body weight (only in males). The latter circumstance evidences a greater damaging action of prolonged self-stimulation on the females' body.

[Features of the effects of apomorphine on rats of different sexes preferring ethyl alcohol]. / Osobennosti deistviia apomorfina na krys raznogo pola, predpochitaiushchikh étilovyi spirt.

The influence of apomorphine (1 mg/kg/day subcutaneously) on the behavior and some pharmacokinetic parameters of both male and female rats preferring ethanol to water was studied experimentally. Upon withdrawal of ethanol, apomorphine decreased the time of transmission to water consumption in the rats of both sexes and prevented a decline in the endogenous ethanol levels, the latter effect being especially pronounced in the female rats. Investigations on the "Animex" actograph showed an intensified response to apomorphine in rats preferring ethanol, with female rats displaying a greater change in the response. Under conditions of a renewed access to ethanol, apomorphine increased the time of the restoration of the previous preference for ethanol to water (with a stronger effect seen in females) and lowered the rate of ethanol elimination from the blood (in the female rats exclusively). The effacement of the sex differences in ethanol addicted rats, and a greater damaging impact of ethanol on female rats are emphasized.

[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.

[Ethanol pharmacokinetics in narcotic action and endogenous ethanol in female rats]. / Farmakokinetika étanola pri narkoticheskom deistvii i éndogennyi étanol u krys-samok.

Experiments were made on female rats to demonstrate a positive correlation between the time of ethanol anesthesia in estrus and diestrus and (1) subsequent preference of ethanol to water (r = 0.68) and (2) ethanol consumption dosage (r = 0.72). In the same rats (during estrus and diestrus), the endogenous level and blood concentrations of ethanol were measured 30 minutes after administering the anesthetic dose (4.5 g/kg) and during the animal's "egress" from anesthesia. The low level of endogenous ethanol and rapid decrease of the blood ethanol concentration upon administering the anesthetic dose during estrus were characteristic of those female rats which, under the conditions of free choice, preferred ethanol to water and consumed it in large doses.

[Significance of the sex differences of experimental animals for ethanol and acetaldehyde pharmacokinetics]. / Znachenie polovykh razlichii éksperimental'nykh zhivotnykh dlia farmakokinetiki étanola i atsetal'degida.

Studies of the pharmacokinetics of ethanol in the blood and exhaled air and of acetaldehyde in exhaled air in rats of different sexes have shown that in the group of normal animals, the level of endogenous ethanol and maximal blood concentration of ethanol administered in the test dose (2.2 g/kg) was higher in females than in males. The decrease of ethanol concentration in the blood and exhaled air proceeds more rapidly in males, the content of acetaldehyde in exhaled air being elevated in all the animals. In the groups of animals preferring ethanol to water, the importance of sex differences as regards the parameters under study reduces, with changes in ethanol pharmacokinetics being more distinctive in females. Unlike normal animals, the decrease of ethanol concentration in the blood and exhaled air in alcoholized rats also entails diminution of acetaldehyde content in exhaled air. After ethanol withdrawal its endogenous level considerably drops, reaching the same level in females and males.

The effect of neuroleptics, tranquillizers, narcotics, antidepressants and anticonvulsive drugs on the alterations of mouse behaviour caused by acetaldehyde.

In a study of the effect of 26 psychoactive drugs on the complex of mouse behaviour changes caused by acetaldehyde it was found that tranquillizers, hypnotics, sodium oxybutyrate and ethanol are the most efficient. The differences in teh drug effects were determined by a tan alpha criterion. Antidepressants and neuroleptics have equal tan alpha, whereas narcotics, anti-convulsive drugs and tranquillizers all have similar tan alpha, but greater than that of the antidepressants and neuroleptics. A direct dose/effect relationship was found to exist for all the drugs investigated except for neuroleptics and antidepressants. For the latter drugs an increase in dose is followed by an increased effect, which, however, decreases on further increase of the dose. The convulsive syndrome is completely abolished only by tranquillizers and narcotics. Our results are quite in agreement with clinical data about the effectiveness of psychoactive drugs in the treatment of the alcohol abstinence syndrome. The method can be used not only for screening purposes, but also to define the specificity in the action of antialcoholic drugs.

[Role of age in the process of the development of experimental alcoholism in rats of both sexes]. / Rol' vazrasta v protsesse formirovaniia éksperimental'nogo alkogolizma u krys raznogo pola.

It has been shown that under free access to liquids 8% ethanol preference to water is developed more rapidly in sexually immature females and more slowly in sexually immature males as compared to sexually mature rats of the respective sex. Sexually immature animals of both sexes are involved simultaneously in the process of alcoholization. In sexually mature animals the degree of ethanol preference to water measured in grams of consumed alcohol per 1 kg body weight is 2--3 times greater than that in sexually mature ones and decreases with age. In sexually immature animals of both sexes the degree of ethanol preference in females significantly exceeds that in males at the onset of preference development while in sexually mature rats such a predominance can be ascertained only after the preference development has been completed.

[Relationship between sex and the development and course of experimental chronic alcoholism]. / Osobennosti formirovaniia i techeniia éksperimental'nogo khronicheskogo alkogolizma v zavisimosti ot pola.

The existence of sex differences in the development and course of experimental alcoholism in sexually mature rats (with 20 individual animals of each sex) was established. With formation of preference to a 8% ethanol solution as against water, with free access of the animals to the liquids, this process by its speed is shown to proceed quicker in males, but the females display a greater degree of preference. Moreover, the females manifest a greater lability with respect to the fortifying properties of ethanol. In framing the preference the presence of a second animal of the same or the other sex leads to a greater consumption of ethanol by the females than by males. On a repeated offering of ethanol following its cancellation the renewed preference of ethanol to water occurs in females quicker and more intensively than in males.

[Effect of several psychotropic agents on changes in the behavior of mice induced by acetaldehyde]. / Vliianie nekotorykh psikhotropnykh sredstv na izmeneniia povedeniia myshei, vyzyvaemye atsetal'degidom.

Results of a study on the effect produced by 26 psychotropic agents on a complex set of behavioral changes in mice induced by introduction of acetaldehyde are presented. Experiments were conducted according to the method of Ortiz et al. (1973) who have proposed this test as a model of the abstinence syndrome. The effect of the agents was evaluated by removal of convulsions according to the Goldstein 4-point scale system (1972). In this respect the most effective proved tranquilizers, hypnotics, sodium oxybutyrate and ethanol. Little effective were neuroleptics and antidepressants. The model may be used in the screening of drugs when treating the abstinence syndromes in chronic alcoholism.