The antinociceptive effect of morphine is reversed by okadaic acid in morphine-naive but not in morphine-tolerant mice.
The activation of specific subtypes of serine/threonine protein phosphatases (PPs) plays a role in the antinociceptive effect of acute morphine, but it is not known whether these enzymes are involved in morphine-induced antinociception in morphine-tolerant animals. We evaluated the effects of both okadaic acid (a selective inhibitor of some serine/threonine PPs) and its inactive analogue L-norokadaone on the antinociception induced by morphine in morphine-naive and -tolerant female mice in the tail-flick test. Okadaic acid (0.01 and 1 pg/mouse, i.c.v.), but not L-norokadaone (1 pg/mouse, i.c.v.), antagonized in a dose-dependent way the antinociception induced by morphine (1-16 mg/kg, s.c.) in morphine-naive animals. However, both okadaic acid (0.01 and 1 pg/mouse, i.c.v.) and L-norokadaone (1 pg/mouse, i.c.v.) were unable to modify the antinociceptive effect of morphine in morphine-tolerant mice. These results suggest that in morphine-induced thermal analgesia, the role of serine/threonine PPs highly sensitive to okadaic acid is different in morphine-tolerant and morphine-naive female mice.
Ocaña
María
M
Department of Pharmacology and Neuroscience Institute, School of Medicine, University of Granada, Avenida de Madrid 12, E-18012 Granada, Spain.
Entrena
José M
JM
Baeyens
José M
JM
Del Pozo
Esperanza
E
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007276:Injections, Intraventricular; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D019319:Okadaic Acid; D009020:Morphine