Inhibition of nitric oxide synthase attenuates the development of morphine tolerance and dependence in mice.
The effect of the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 5-20 mg/kg i.p.) and NG-nitro-L-arginine (NO2Arg, 5-20 mg/kg i.p.) on morphine-induced analgesia, as well as on morphine induced tolerance and dependence was examined in male albino Swiss mice. Neither acute nor repeated (for 5 days) administration of the nitric oxide synthase inhibitor, L-NAME affected the morphine induced analgesia, as measured by hot plate and tail-flick tests. On the other hand, administration of L-NAME or NO2Arg along with morphine prevented the development of tolerance to the analgesic effect of morphine for at least 7 days, whereas the analgesic effect of morphine alone disappeared after 5 days. L-NAME and NO2Arg also attenuated some signs of morphine dependence, as assessed by naloxone (2 mg/kg)-precipitated withdrawal. These results indicate that NO may play a role in the development of morphine tolerance and dependence.
Majeed
N H
NH
Neuropeptide Research Department, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Przewłocka
B
B
Machelska
H
H
Przewłocki
R
R
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology / Q000517:prevention & control; D019331:NG-Nitroarginine Methyl Ester; D009270:Naloxone / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine
D019335:Nitroarginine; D009569:Nitric Oxide; D009270:Naloxone; D009020:Morphine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester