The response of rat brain protein synthesis to ethanol and sodium barbital

Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from "Control," "Ethanol" and 24 h "Ethanol Withdrawn" rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of 14(C) leucine into protein by all three groups of ribosomes. Under these conditions, the "Ethanol Withdrawn" group displayed the largest inhibition of the 14(C) leucine incorporation into protein when compared to the "Control" and "Ethanol" groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of 14(C) leucine into protein by "Control" and "Ethanol" polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units.