Reversal by naloxone of the effects of chronic administration of drugs of dependence on rat liver and brain tryptophan metabolism.

1. Chronic administration of ethanol, morphine, nicotine or phenobarbitone has previously been shown to enhance rat brain 5-hydroxytryptamine (5-HT) synthesis by increasing the availability of circulating tryptophan to the brain secondarily to the NADPH-mediated inhibition of liver tryptophan pyrrolase activity. 2. Naloxone reverses the above enhancement of 5-HT synthesis and the accompanying increase in tryptophan availability to the brain and the inhibition of liver tryptophan pyrrolase activity. 3. It is suggested that naloxone exerts these effects by antagonizing the chronic drug-induced increase in liver [NADPH]. 4. Naloxone increases serum corticosterone concentration in rats chronically treated with the above four drugs of dependence. Possible explanations of this effect are discussed.