Mediation of nitric oxide in inhibitory effect of morphine against electroshock-induced convulsions in mice.
Nitric oxide (NO) and morphine have been coupled in many physiological as well as pathological processes. The present study examined the involvement of the L-arginine/NO pathway in the anticonvulsant properties of systemic morphine (2-30 mg/kg) against electroshock seizures (ECS) in mice. Morphine decreased the intensity of maximal electroshock seizures (MES) and increased the threshold for ECS. Neither the NOS substrate L-arginine (30, 60, and 100 mg/kg), the reversible nonspecific NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 3, 10, and 30 mg/kg), the irreversible specific inducible NOS inhibitor aminoguanidine (20, 50, and 100 mg/kg), nor the opioid receptor antagonist naloxone (0.1, 0.3, and 1 mg/kg) did alter per se the ECS threshold or the intensity of MES at doses used. However, both naloxone and L-NAME, but not aminoguanidine, inhibited the anticonvulsant effects of morphine (30 mg/kg) against ECS, while L-arginine potentiated the anticonvulsant effects of lower doses of morphine (2 or 10 mg/kg). Low doses of naloxone (0.1 or 0.3 mg/kg) or L-NAME (3 mg/kg), which did not alter morphine effect per se, showed additive anticonvulsant effects against MES. Thus, the L-arginine/NO pathway seems to play a role in the anticonvulsant properties of morphine against ECS and this mediation involves the constitutive, but not the inducible, form of nitric oxide synthase.
Khavandgar
Simin
S
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Homayoun
Houman
H
Dehpour
Ahmad Reza
AR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004597:Electroshock / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009020:Morphine