Central action of narcotic analgesics. IX. Participation of serotonin in the development of tolerance to cataleptogenic effects of morphine in rats.

Subcutaneous implantation of morphine-base (75 mg) pellets over a period of 72 h caused the development of tolerance ot cataleptogenic action of morphine in rats. The development of morphine tolerance was inhibited by p-chlorophenylalanine (pCPA) or reserpine, drugs which decrease the content of brain serotonin (5-HT). Administration of 5-hydroxytryptophan (5-HTP(, which protected 5-HT stores against depleting action of reserpine, prevented the above of reserpine on the development of morphine tolerance in rats. Blockade of 5-HT neurotransmission by pizotifen or cyproheptadine inhibited the development of morphine tolerance, while the increase of it by imipramine did not alter the development of this tolerance . The Obtained results have shown that serotonergic system plays an important role in the development of tolerance to cataleptogenic effects of morphine.