Abstract
Ethanol exerts a variety of effects on tryptophan and 5-hydroxytryptamine (5-HT) metabolism in man and in experimental animals. In rat models. whose tryptophan metabolism is nearest to that of man, chronic ethanol administration enhances brain 5-HT synthesis whereas inhibition of synthesis occurs during the subsequent withdrawal period. Both effects are caused by corresponding changes in tryptophan availability to the brain and are thought to be due to inhibition and enhancement of liver tryptophan pyrrolase activity respectively. It has been suggested that ethanol acts chronically by inhibiting apo-tryptophan pyrrolase synthesis. We have studied the relationship between tryptophan pyrrolase activity and the expression of hepatic tryptophan pyrrolase mRNA in rats chronically administered ethanol by means of an ethanol-containing liquid diet. Wistar rats were fed ethanol diet at concentrations of 5% and 8% (v/v) and for duration's of two and four weeks. Rats were withdrawn in a starved state for seven hours by which time there were demonstrable signs of withdrawal. Matched controls were fed equal amounts of isocaloric ethanol-free liquid diet. The livers were removed from each of the animals and both tryptophan pyrrolase activity and synthesis were measured. Tryptophan pyrrolase activity was decreased before withdrawal and greatly increased over baseline following withdrawal.
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