Effect of narcotics on the uptake of serotonin precursors by the rat brain

The extraction of 14C-tryptophan and 14C-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 a increase in that of 5-HTP. Naloxone alone had no effect on the extraction of either tryptophan or 5-HTP but completely blocked the effect of 20 mg/kg of morphine on the extraction of both tryptophan and 5-HTP. In contrast to acute treatment with morphine, the extractions of tryptophan 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 increased and dextrorphan had no effect on the extraction of 5-HTP. These results suggest that an increase in the rate of central serotonin synthesis after acute treatment 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 increased uptake of tryptophan.