The synthesis rate and turnover time of 5-hydroxy-tryptamine in brains of rats treated chronically with morphine.

1. Four schedules of subcutaneous pellet implantation were used to induce tolerance to and physical dependence on morphine in Sprague-Dawley rats. 2. The schedules included implantation of four morphine pellets (each containing 75 mg of morphine free base) during a 3 day period (schedule 1); six pellets during 3 days (schedule 2); six pellets during 7 days (schedule 3) and ten pellets during a 10 day period (schedule 4). 3. A high degree of tolerance and dependence on morphine, comparable to that induced in mouse by implantation of a single morphine pellet for 3 days, was produced with schedule 4. 4. Brain 5-hydroxytryptamine (5-HT) turnover rates as measured by rate of accumulation of 5-HT after monoamine oxidase inhibition by pargyline were not different in rats rendered tolerant to and dependent on morphine according to schedules 1 to 4 when compared with corresponding placebo pellet-implanted rats. 5. The turnover rates of 5-HT in brain of morphine-and placebo pellet-implanted rats (schedule 4) from which the pellets had been removed for 24 h were also similar. 6. It is concluded that tolerance to, and physical dependence upon morphine in the rat is not associated with changes in brain 5-HT dynamics.