Brain metabolite concentrations and redox states in rats fed diets containing 1,3-butanediol and ethanol

Both ethanol and its dimer 1,3-butanediol (BD) are substrates for alcohol dehydrogenase in liver and thus have many similar effects upon metabolite concentrations and redox states in that organ. Although the mechanism by which ethanol exerts its effects on the brain is not known, it must differ from that in liver since brain contains insignificant amounts of alcohol dehydrogenase. The effects of BD, which does not produce intoxication, and ethanol upon brain were compared in an attempt to determine which changes in metabolite content are related to depression of the CNS. Diets containing 47% of calories as ethanol, BD, or glucose were pair-fed to rats for 62 days. The brains were then removed and frozen with a new apparatus which prevents postmortem changes, and concentrations of metabolites were determined. Substitution of BD for glucose in the diet caused a decrease in the brain content of glucose, lactate and α-oxoglutarate and an increase in glutamate and citrate. Substitution of ethanol for glucose caused only a decrease in the brain content of glucose and an increase in citrate. The ethanol diet, as compared with the BD diet, caused an elevation of the brain content of glucose and a decrease in glutamate. Both BD and ethanol caused a decrease in the free cytoplasmic $\text{NADP}{}^{\mathrm{+}}\text{]}\text{NADPH}\text{]}$ ratio in brain without changing the $\text{NAD}{}^{\mathrm{+}}\text{]}\text{NADH}\text{]}$ of cytoplasm or mitochondria.Except for the differences in effect upon glucose and glutamate, BD and ethanol appear to act similarly on the metabolite content of rat brain. It is therefore concluded that the brain is resistant to changes of the measured metabolites during the process of chronic ethanol ingestion. It is further suggested that the small changes observed in the cytoplasmic $\text{NADP}{}^{\mathrm{+}}\text{]}\text{NADPH}\text{]}$ ratio after ethanol feeding are not related to the depression of CNS activity associated with ethanol ingestion since they also occur after feeding BD.