Abstract

The rate of serotonin (5-HT) synthesis in the brains of mice rendered tolerant to and physically dependent on morphine either by s.c. implantation of a morphine pellet for three to four days or by daily s.c. injections of increasing doses of morphine was found to be about twice that of control animals receiving a placebo implant or daily saline injections. Inhibition of brain 5-HT synthesis by p-chlorophenylalanine was accompanied by a decrease in tolerance and dependence development to morphine. The concomitant administration of naloxone to reduce tolerance and physical dependence development to daily injections of morphine resulted also in a decrease in the rate of brain 5-HT synthesis. Although the roles of other biogenic amines have not been excluded, the results suggest that increased brain 5-HT synthesis may be associated with tolerance and physical dependence development to morphine in the mouse but do not establish a causal relationship.