Central action of narcotic analgesics. VII. The role of serotonin in the development of morphine tolerance in the locomotor activity test in mice and rats.

The development of tolerance to morphine-induced motor activity of mice and rats, as well as the influence of drugs which alter the brain serotonergic functions on the development of morphine tolerance was studied. Tolerance to morphine was induced by subcutaneous implantation of morphine-base pellets. After 72 h pellets were removed and 6 hr later motility was tested. Implantation of morphine pellets caused the development of tolerance to morphine-induced motor activity of mice and rats. Development of morphine tolerance was inhibited in mice and rats by p-chlorophenylalanine (pCPA) or reserpine, drugs which decrease content of brain serotonin. 5-hydroxytryptophan (5-HTP) inhibited the above effect of pCPA in mice, while tryptophan did not. Administration of 5-HTP, which protected serotonin stores against depleting action of reserpine decreased inhibiting action of reserpine on the development of morphine tolerance in rats. Although cyproheptadine and pizotifen did not alter the development of morphine tolerance in rats, nevertheless, it seems from these results that serotonin neurotransmission is of some importance in the development of tolerance to morphine.