Further evidence that nitric oxide modifies acute and chronic morphine actions in mice.
The effects of the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA, 2.5-10 microg i.c.v.), and the NO synthesis precursor, L-arginine (L-Arg, 2.5-10 microg i.c.v.), on morphine-induced analgesia, and on morphine-induced tolerance and dependence were examined in mice. Administration of L-NNA diminished the morphine-induced analgesia. L-Arg pretreatment increased the analgesic effect of morphine. Repeated pretreatment (three times, at 24-h intervals) with L-NNA diminished both acute and chronic tolerance to morphine, whereas both the acute and the chronic morphine-induced tolerance increased after the repeated (three times, at 24-h intervals) administration of L-Arg. Neither L-NNA nor L-Arg affected the signs of morphine dependence, as assessed by naloxone (1 mg/kg, s.c.)-precipitated withdrawal. Our data suggest that increased NO synthesis potentiates morphine analgesia and enhances the development of morphine tolerance in mice.
Pataki
I
I
Department of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Telegdy
G
G
D000698:Analgesia; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004361:Drug Tolerance / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D019001:Nitric Oxide Synthase