SYNTHESIS RATE AND TURNOVER TIME OF 5-HYDROXYTRYPTAMINE IN BRAINS OF RATS TREATED CHRONICALLY WITH MORPHINE

Four schedules of subcutaneous pellet implantation were used to induce tolerance to and physical dependence on morphine in Sprague‐Dawley rats. 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). 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. 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. 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. It is concluded that tolerance to, and physical dependence upon morphine in the rat is not associated with changes in brain 5‐HT dynamics. 1979 British Pharmacological Society