Influence of Ketosis and Glycemia Levels on Craving for Ethanol in Alcoholized Rats

Abstract

Relevance. In case of developed alcoholic disease, under conditions of alcoholic hypoglycemia, ketone bodies act as an energy substrate for the brain. However, the role of ketone hunger for maintaining the craving for alcohol has not been established. The assumption of such a connection has a right to exist, since it is alcohol that stimulates the formation of ketone bodies. Therefore, with developed alcoholism, the desire to consume alcohol (and, in fact, "saturate" the brain with ketone bodies) can be considered as a consequence of hypoketonemia. Accordingly, the hunger of the alcoholic is the result of hypoketonemia, but not hypoglycemia. Therefore, it is relevant to conduct a study in which the given variables (controlled by us) were the level of glycemia and the level of ketonemia, and the amount of alcohol consumed voluntarily (under conditions of free choice) was a derivative and dependent value.
 Objective: to study the relationship between craving for alcohol, and levels of glycemia and ketonemia in alcoholized rats.
 Materials and methods. Male white rats (n = 40) were forcibly alcoholized with 10% ethanol in 16 weeks. After that, for 30 days, they had a free choice of three types of drinking: clean water, 5% glucose, and 10% ethanol. The volume of consumed liquids was recorded. The criterion for the developed alcohol dependence was the preference of ethanol. At this stage, the animals were divided into 4 groups. Rats were injected per os with 0.8-1.5 ml of: 1.4% unitiol (3.5 mg / kg) to suppress ketonemia – group 1 (n = 10); 40% starch (1.0 g / kg) to eliminate hypoglycemia – group 2 (n = 10); 2.8% unitiol and 80% starch to suppress ketonemia and eliminate hypoglycemia – group 3 (n = 10); 0.9% NaCl as a control – group 4 (n = 10). Blood glucose (from the tail vein) and urine ketone bodies were monitored. The glucose level was determined with a glucometer. Test strips were used to detect ketone bodies in urine. The results were processed with MedStat software. To measure the strength of the correlation between the indicators, Spearman and Pearson tests were used.
 Results. No ketone bodies were found in the urine of healthy animals; however, after the end of forced alcoholization, varying levels of ketonuria were recorded in all rats: from 0.5 to 10 mmol / L (Spearman's rank correlation test was 0.8). Glycemia in healthy rats was 7.0 ± 1.4 mmol / L. After alcoholization, it decreased (p <0.001) to 3.0 ± 0.7 mmol / l. Ethanol consumption during first 10 days of forced alcoholization was 3.2 ± 0.7 ml per 100 g of animal weight; by the end of the third week - 4.9 ± 1.1 ml; by the end of the sixth week - 6.4 ± 1.4 ml (this was a climax of consumption, since consumption did not increase up to the 16th week).
 After a 30-day correction, the level of glycemia (mmol / L) was as follows: animals of the 1st group (unitiol) - 4.0 ± 0.8; animals of the 2nd group (enhanced carbohydrate diet) - 7.1 ± 1.2; animals of the 3rd group (unitiol + enhanced carbohydrate diet) - 7.1 ± 1.1; animals of the 4th group (0.9% NaCl) - 3.5 ± 0.8.
 Alcohol consumption (ml per 100 g of animal weight) after 30-day correction was as follows: in group 1 (unitiol) - 5.1 ± 0.9; in group 2 (enhanced carbohydrate diet) - 2.7 ± 1; in group 3 (unitiol + enhanced carbohydrate diet) - 3.5 ± 1.5; in group 4 (0.9% NaCl) - 4.5 ± 1.2.
 A positive strong correlation was found between ethanol consumption and a decrease in glycemia (Pearson's test – 0.8).
 Conclusion. In alcoholized animals with severe hypoglycemia and ketosis, drug suppression of ketosis does not reduce the craving for ethanol. Metabolic correction, aimed at eliminating hypoglycemia, helps to reduce alcohol consumption and reduce the severity of ketosis. The reason for maintaining a stable craving for alcohol is the metabolic demand of the brain for ketone bodies, as alternative food sources in conditions of alcoholic hypoglycemia, and the synthesis of which is stimulated by alcohol intake.