Printed in USA. EFFECT OF NARCOTICS ON THE UPTAKE OF SEROTONIN PRECURSORS BY THE RAT

Abstract

LARSON, ALICE A. AND A. E. TMoRI: Effect of narcotics on the uptake of sero-tonin precursors by the rat brain. J. Pharmacol. Exp. Ther. 200: 216-223, 1977. The extraction of 14C-tryptqphan and ‘4C-hydroxytryptophan (5-HTP) from the blood to the brain was measured using an indicator dilution technique. Acute treatment with morphine caused a dose-related decrease in the extraction of tryptophan by the brain and an increase in that of5-HTP. Naloxone alone had no effect on the extraction of either tryptophan or 5-HIP but completely blocked the effect of 20 mg/kg of mor-phine on the extraction of both tryptophan and 5-HTP. In contrast to acute treatment with morphine, the extractions oftryptophan and 5-HTP were not significantly altered 48 hours after chronic treatment with morphine. The extraction of 5-HTP remained unchanged and that of tryptophan increased significantly 72 hours after chronic morphine treatment. In equivalent doses, levorphanol decreased the extraction of tryptophan more than its inactive isomer, dextrorphan, whereas levorphanol in-creased and dextrorphan had no effect on the extraction of 5-HTP. These results sug-gest that an increase in the rate of central serotonin synthesis after acute treat-ment with morphine may be due to an increased uptake of 5-HTP from the blood to the brain while that after chronic treatment with morphine may be due to an in-creased uptake of tryptophan. Attempts to correlate changes in the rate of turnover of 5-hydroxytryptamine (serotonin or 5-HT) with morphine analgesia and the devel-opment of tolerance have yielded observations of either increases in serotonin turnover during narcotic analgesia (Haubrich and Blake, 1969

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