Effects of 5-HT receptor antagonists on morphine-induced tolerance in mice.
The effect of 5-HT receptor antagonists on tolerance to morphine antinociception was studied in mice. Slow release morphine suspension was injected subcutaneously (s.c.) in order to produce tolerance. When different doses of morphine (3, 6 and 9 mg/kg) were administered on the 4th day after injection of slow-release morphine suspension, tolerance to the test doses of morphine was observed. The tolerance obtained was decreased by pretreatment with the non-selective 5-HT receptor antagonist methysergide (1 and 2 mg/kg) or the 5-HT2 receptor antagonist ritanserin (1 and 2 mg/kg). When the 5-HT receptor antagonists were used on the 2nd and 3rd day after injection of slow-release morphine suspension or on the 4th day (60 min before last dose of morphine), a maximum reduction in morphine tolerance was observed on the 3rd day. Pretreatment 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 morphine antinociception.
Zarrindast
M R
MR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Sajedian
M
M
Rezayat
M
M
Ghazi-Khansari
M
M
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003692:Delayed-Action Preparations; D004361:Drug Tolerance; D007279:Injections, Subcutaneous; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000700:Analgesics; D003692:Delayed-Action Preparations; D012702:Serotonin Antagonists; D016713:Ritanserin; D008711:Metergoline; D008803:Mianserin; D009020:Morphine; D008784:Methysergide