The involvement of endogenous opioids and nitricoxidergic pathway in the anticonvulsant effects of foot-shock stress in mice.
The involvement of endogenous opioids and nitric oxide (NO) in the anticonvulsant effects of stress against pentylenetetrazole (PTZ)- or electroconvulsive shock-induced seizures was assessed in mice. The prolonged and intermittent foot-shock stress, which induced opioid-mediated analgesia, had significant protective effects against both seizure types which was reversible by naloxone (0.3, 1 or 2 mg/kg), while brief and continuous foot-shock did not alter the seizure susceptibility. Pre-treatment with non-specific nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 1, 2, 5, 10 or 30 mg/kg), but not with specific inducible NOS (iNOS) inhibitor, aminoguanidine (50 or 100 mg/kg), blocked the stress-induced anticonvulsant effects. The lower doses of naloxone (0.3 mg/kg) and L-NAME (2 mg/kg) showed additive effects in blocking the stress-induced anticonvulsant properties. L-arginine at a per se non-effective dose of 20 mg/kg potentiated the stress-induced anticonvulsant properties, an effect which was inhibited by L-NAME but not by aminoguanidine. Furthermore, a low dose of morphine (0.5 mg/kg) showed potentiation with stress in increasing PTZ seizure threshold. This potentiation was reversed by either naloxone or L-NAME at low doses but not by aminoguanidine. Taken together, these results show that NO synthesis, through constitutive but not iNOS, is involved in opioid-dependent stress-induced anticonvulsant effects against electrical and PTZ-induced convulsions.
Homayoun
Houman
H
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Khavandgar
Simin
S
Dehpour
Ahmad Reza
AR
D000818:Animals; D003292:Convulsants; D004056:Differential Threshold; D004198:Disease Susceptibility; D004597:Electroshock; D004723:Endorphins / Q000502:physiology*; D005528:Foot; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010146:Pain / Q000209:etiology; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*
D003292:Convulsants; D004723:Endorphins; D009294:Narcotics; D009569:Nitric Oxide; D009020:Morphine; D010433:Pentylenetetrazole