Lithium inhibits the modulatory effects of morphine on susceptibility to pentylenetetrazole-induced clonic seizure in mice: involvement of a nitric oxide pathway.
Lithium has been reported to inhibit opioid-induced properties. The present study examined the effect of acute and chronic administration of lithium chloride (LiCl) on morphine's biphasic modulation of susceptibility to pentylenetetrazole (PTZ)-induced clonic seizure in mice. We also examined the possible involvement of nitric oxide (NO) pathway in lithium effect. Both acute (0.1 and 1 mg/kg) and chronic (same doses, 21 consecutive days) administration of LiCl completely inhibited the anticonvulsant and proconvulsant effects of morphine (at doses 1 and 30 mg/kg, respectively). A very low and per se noneffective dose of LiCl (0.05 mg/kg) significantly inhibited both phases of morphine effect when administered concomitant with a noneffective low dose of naloxone (0.1 mg/kg). The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) at a per se noneffective dose of 0.3 mg/kg potentiated the inhibitory effects of low doses of LiCl (0.01 and 0.05 mg/kg) on both phases of morphine effect. l-arginine, a NO synthase substrate, at a per se noneffective dose of 30 mg/kg reversed the inhibitory effects of lithium (1 mg/kg). Lithium is capable of antagonizing both modulatory effects of morphine on seizure susceptibility even at relatively low doses. These inhibitory effects of lithium may also involve NO synthesis.
Honar
Hooman
H
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Riazi
Kiarash
K
Homayoun
Houman
H
Demehri
Shadpour
S
Dehghani
Mehdi
M
Vafaie
Kourosh
K
Ebrahimkhani
Mohammad Reza
MR
Rashidi
Narges
N
Gaskari
Seyed Ali
SA
Dehpour
Ahmad Reza
AR
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D004056:Differential Threshold / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009292:Narcotic Antagonists; D009569:Nitric Oxide / Q000378:metabolism*; D010433:Pentylenetetrazole; D011957:Receptors, Opioid / Q000819:agonists; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000927:Anticonvulsants; D003292:Convulsants; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine; D018021:Lithium Chloride; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole