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Abstract
Chronic administration of four drugs of dependence (ethanol, morphine, nicotine and phenobarbitone) enhances rat brain 5-hydroxytryptamine synthesis, whereas subsequent withdrawal causes an inhibition. These opposite effects are caused by correspondingly opposite changes in tryptophan availability to the brain brought about by altered hepatic catabolism of tryptophan by the action of liver tryptophan pyrrolase. The metabolism and disposition of an exogenously administered tryptophan load are also altered in similar fashions. The results are discussed briefly in relation to the role of liver tryptophan pyrrolase in depressive illness and the possible involvement of tryptophan and 5-hydroxytryptamine in drug dependence.
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