Influence of the immunization against heterologous alcohol dehydrogenase on liver alcohol dehydrogenase isozymes and alcohol abuse of rats.

The possible biochemical and immunological mechanisms of the previously discovered phenomenon of significant and prolonged decrease of alcohol abuse of albino rats after the intravenous injection of the heterologous alcohol dehydrogenase (ADH) were studied. It was found that immunization of rats against horse liver S-ADH result in the appearance of a high titre of antibodies against rat liver ADH-3 isozyme. This isozyme is responsible for the metabolism of 90% of alcohol administrated in vivo. It is shown that immunization against horse liver S-ADH leads also to a significant (2--3-fold) lowering of the activity level of ADH-3 in rat liver. The activity level of the other rat ADH isozymes, ADH-1 and ADH-2, was not found to be changed. The intravenous injection of the specific anti-(horse liver S-ADH) serum, purified by affinity chromatography on immobilized horse liver S-ADH, resulted in a significant decrease of alcohol abuse in alcohol-dependent animals. These results allow us to assume an important role of rat liver ADH-3 in the mechanism of alcohol addiction.