Methodological problems in the search for antialcoholic remedies (literature review)

Abstract

Methods used currently in the treatment of alcoholism, such as conditioned reflex therapy, the creation of intolerance, sensitization to alcohol by the use of disulfiram, etc., are unsatisfactory to clinicians because they are not sufficiently effective, and also because of serious side effects and complications which accompany treatment with drugs like disulfiram. Medicines are needed which are more effective and have a wider range of therapeutic activity. The massive search for new antialcoholic substances is quite possible under conditions of well-designed animal experiments. Nevertheless, the experimental methods for searching for such substances are virtually undeveloped. Models of chronic alcoholism in animals, used advantageously in the study of the pathogenesis of this illness, are not always satisfactory for screening antialcoholic drugs. It is therefore appropriate to consider the basic studies of this subject in developing the most efficient directions for experimental selection of new antialcoholic drugs. In screening studies, one must attempt to satisfy the following requirements: 1) models of chronic alcoholism should develop the disorder in a comparatively short time; 2) the experiments should be easily and precisely reproducible and should have clearly quantitative characteristics permitting comparison in the presence of several variables, of which the medication is one. Analysis of the experimental data of different investigators illustrates the necessity of meeting certain conditions in establishing models of chronic alcoholism. One of the most important conditions is the correct choice of experimental animals. Different animal species are not equally easily induced to develop alcohol addiction. The Finnish investigators, Arvola and Forsander [1, 2] compared the ability to develop alcohol addiction in six animal species: hedgehog, golden hamster, guinea pig, rabbit, white rat, and mouse. The consumption of a 10% solution of ethanol was studied under conditions of free choice. The golden hamster consumed the largest quantity of alcohol, the guinea pig the least. The hamster also most sharply distinguished solutions with lower alcohol concentrations, and also freely consumed alcohol solutions of a wide range of concentrattens. Komura et al. [3], came to analogous conclusions and, furthermore, established a correlation between alcoholic consumption by animals and the activity level of alcohol dehydrogenase in the liver. In their experiments additional alcohol consumption was easily developed in golden hamsters and some strains of mice. These animals had the highest levels of alcohol dehydrogenase activity, while guinea pigs had a low level of alcohol consumption and of enzyme activity. The authors suggest the use of these criteria in the selection of animals as experimental models for chronic alcoholism. Although experiments have been conducted successfully on various animals and birds, including monkeys, dogs, miniature pigs, pigeons, etc., most studies show a preference for working with traditional laboratory animals, rats and mice. For these it is necessary to specify the strain, the sex, and the age of the animals, the conditions under which they are maintained, and their diet. Numerous studies have shown that addiction is most easily developed in mice of the C57B1 strain and its hybrids. Mice of the KR and DBA strains avoid Consuming alcohol. Such a relationship to alcohol can de