Drinking and Hedonic Behavior of Alcoholized Rats

Abstract

Relevance. To relieve alcohol withdrawal syndrome, intravenous infusion of glucose and antidotes to neutralize ketone bodies is used. But after treatment, the craving for alcohol remains, and relapses of alcohol consumption are observed in 60-90% of patients. It remains unclear if there is a connection between hypoglycemia, ketosis, on the one hand, and the craving for alcohol consumption, on the other hand.
 Objective: to find out the effect of glycemic level normalization and prolonged maintenance of normal blood glucose concentration on ethanol consumption in alcoholized rats. At the same time, we have chosen two alternative ways to eliminate hypoglycemia: 1) by providing animals with unlimited access to a water trough filled with glucose solution; 2) by forced feeding of animals with a high-carbohydrate diet.
 Materials and methods. 70 rats were housed in the individual cages. First, two water troughs were placed in each cage for one week: the first one was filled with pure water and another one contained 5% glucose solution. Second, forced alcoholization of rats was performed by leaving one trough filled with 10% ethanol solution in each cage. Duration of alcoholization was different: 3 weeks for the 1st group of rats (n=20), 6 weeks for the 2nd group of animals (n=20), and 16 weeks for the 3rd group of rats (n=20). Animals of the control group (n=10) received pure water. Third, after forced alcoholization, animals of the experimental groups had free access to three different troughs for three weeks: the first trough was filled with pure water, the second one – with 5% glucose solution, and the third one contained 10% ethanol solution. Rats of the control group were able to choose between water and 5% glucose solution. At the third stage, animals of the experimental groups were divided into two subgroups with 10 rats in each one. Animals of one of the subgroups from each experimental group were kept on a high-carbohydrate diet: they were administered 1 ml of 40% starch kissel (2.0 g/kg, in terms of glucose) per os 3 times a day. The volumes of all consumed fluids were recorded daily throughout the experiment. The results were processed using the MedStat program. 
 Results. Healthy rats drank 2.5±0.6 ml of water and 1.6±0.6 ml of glucose solution per 100 g of body weight daily. In the first 7 days of forced alcoholization, the animals drank 3.1±0.7 ml of ethanol solution per 100 g of body weight. By the end of the third week, consumption of ethanol solution increased up to 4.9±0.8 ml per 100 g of body weight (p<0.001), which indicated development of adaptation. By the end of the sixth week, there was a prominent elevation of ethanol consumption up to 6.4±0.9 ml per 100 g of body weight, and the total volume of consumed alcohol solutions was 1.3 times higher than that of the third week (p<0.001). At the sixth week of observation, alcohol intake reached its climax, since further alcoholization up to 16 weeks did not lead to any changes in drinking behavior (p=0.712). We consider that the minimal duration of forced alcoholization is 6 weeks. During the process of alcoholization, the total daily consumption of fluids by animals was increasing, compared to healthy rats, and, by the end of the 16th week, it exceeded the indicator of healthy rats by 1.8 times. In alcoholized rats, glucose loses its hedonic properties. By the end of the 16th week of alcoholization, under the condition of free choice of drinks, glucose consumption was 8 times lower than that of in healthy animals. Rats consumed less ethanol if they were receiving an additional high-carbohydrate diet. The duration of metabolic correction with a starch solution is important: the longer it is, the less alcohol craving will be. 
 Conclusions. Alcohol-dependent rats reject the glucose solution offered as a drink. But prolonged and forced administration of glucose leads to a decrease in alcohol consumption.