REVERSAL BY NALOXONE OF THE EFFECTS OF CHRONIC ADMINISTRATION OF DRUGS OF DEPENDENCE ON RAT LIVER AND BRAIN TRYPTOPHAN METABOLISM

Abstract
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.

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