Unchanged Rate of Brain Serotonin Synthesis during Chronic Morphine Treatment and Failure of Parachlorophenylalanine to attenuate Withdrawal Syndrome in Mice

Abstract

IT has recently been reported that the rate of synthesis of brain 5-hydroxytryptamine (serotonin) is raised two to five-fold in mice treated by the chronic administration of morphine1. In such mice the withdrawal syndrome produced by the narcotic antagonist naloxone was attenuated by parachlorophenylalanine (PCPA)1, an inhibitor of tryptophan 5-hydroxylation2 which is the rate limiting step in the synthesis of serotonin. This work1 implicated some function of brain serotonin in the development of physical dependence to morphine. Because of the potential importance of this conclusion both in the field of narcotic drug dependence and by implication in the mechanisms controlling the synthesis of brain serotonin we have attempted to repeat this work. Our investigations do not confirm the previous findings and no evidence has been found to suggest an increased rate of brain serotonin synthesis or of an attenuating effect of PCPA upon the withdrawal syndrome produced by naloxone in mice treated by chronic morphine administration.