Decrease of tolerance development to morphine by 5-hydroxytryptophan and some related drugs

The administration of 5-hydroxytrytophan (5-HTP) produced a hyperalgesic state in mice tolerant to the analgesic action of morphine. This effect was counteracted by p-chlorophenylalanine (p-CPA) which uncovered the analgesic effect of the serotonin precursor, observed in nontolerant animals. 5-HTP administered prior to various doses of morphine decreased tolerance to the opiate. This effect was also observed in animals treated with p-CPA, methysergide or reserpine. The administration of Dopa prior to morphine failed to inhibit development of tolerance to the analgesic. These results provide evidence in favour of the hypothesis that tolerance to morphine is related to a change in serotonin metabolism or reactivity (see Discussion) induced by the analgesic.