The uptake of radiolabeled tryptophan and 5-hydroxytryptophan (5-HTP) by the brain and their conversion to serotonin was simultaneously measured in the rat after injection of the tracers into the carotid artery. Although the uptake of tryptophan by the brain decreased after a single dose of morphine while that of 5-HTP increased, the conversion of both tryptophan and 5-HTP to serotonin increased. A single dose of morphine was also found to decrease the incorporation of tryptophan into brain stem proteins. After the implantation of morphine pellets for 72 hr, the conversion of tryptophan to serotonin was not different from control, while that of 5-HTP to serotonin remained elevated. In rats pretreated with pargyline and injected i.a. with either radiolabeled tryptophan or 5-HTP, the total accumulated radioactivity found in the brain was significantly higher in morphine-tolerant rats than that in pargyline-pretreated control animals. However, the level of total accumulated serotonin formed in these rats was not significantly increased. These results suggest that an increase in the rate of synthesis of serotonin after a single dose of morphine may be caused by an increased uptake of 5-HTP and conversion of both 5-HTP and tryptophan to serotonin. Since the transport of tryptophan from the blood to the brain is decreased after treatment with morphine, the increased availability of tryptophan may be a result of morphine-induced inhibition of protein synthesis in the brain stem. The effect of chronic treatment with morphine on the rate of synthesis of serotonin is interpreted in terms of a functional and a total pool of serotonin in the brain.
|Number of pages
|Journal of Pharmacology and Experimental Therapeutics
|Published - Dec 1 1978