Are glycineB sites involved in the development of morphine tolerance?
Numerous data have indicated that competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists attenuate the development of tolerance to the analgesic effect of morphine. This study extends these findings on the effects of glycine(B) site antagonist, L-701.324. Tolerance to the analgesic effect of morphine was measured in hot-plate test in Wistar rats. For 9 days, animals were first injected with vehicle or glycine(B) receptor antagonist, L-701.324 (2.5 and 5 mg/kg, po). The non-competitive NMDA receptor antagonist, MK-801 (0.05 or 0.1 mg/kg, ip) was used as a reference compound. The injection of L-701.324, MK-801 or saline was followed, 20 min later, by the injection of morphine (10 mg/kg, sc). Hot-plate latencies were determined 20 min after the second injection on odd-numbered days. The results indicated that chronic administration of glycine(B) site antagonist, L-701.324 decreased the analgesic effect of morphine and they may suggest that this substance at both used doses increased the development of morphine tolerance, whereas non-competitive NMDA antagonist, MK-801 at the dose of 0.1 mg/kg potentiated the analgesic effect of morphine and attenuated the development of morphine tolerance.
Kotlińska
J
J
Department of Pharmacodynamics, Medical Academy, Staszica 4, PL 20-081 Lublin, Poland. Jolka@panaceum.am.lublin.pl
D000284:Administration, Oral; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D004361:Drug Tolerance / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011044:Poland; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013997:Time Factors
D015363:Quinolones; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009020:Morphine; C094635:L 701324