EFFECTS OF 5-HT RECEPTOR ANTAGONISTS ON MORPHINE-INDUCED TOLERANCE INMICE

The effect of 5-HT receptor antagonists on tolerance to morphine antin ociception was studied in mice. Slow release morphine suspension was i njected subcutaneously (s.c.) in order to produce tolerance. When diff erent doses of morphine (3, 6 and 9 mg/kg) were administered on the 4t h day after injection of slow-release morphine suspension, tolerance t o the test doses of morphine was observed. The tolerance obtained was decreased by pretreatment with the non-selective 5-HT receptor antagon ist methysergide (1 and 2 mg/kg) or the 5-HT2 receptor antagonist rita nserin (1 and 2 mg/kg). When the 5-HT receptor antagonists were used o n the 2nd and 3rd day after injection of slow-release morphine suspens ion or on the 4th day (60 min before last dose of morphine), a maximum reduction in morphine tolerance was observed on the 3rd day. Pretreat ment of animals with metergoline (1 and 2 mg/kg) or mianserin (1 and 2 mg/kg) also decreased the tolerance to morphine. It may be concluded that at least a 5-HT2 receptor mechanism is involved in tolerance to m orphine antinociception.