Lithium inhibits the modulatory effects of morphine on susceptibility to pentylenetetrazole-induced clonic seizure in mice: Involvement of a nitric oxide pathway

Hooman Honar, Kiarash Riazi, Houman Homayoun, Shadpour Demehri, Mehdi Dehghani, Kourosh Vafaie, Mohammad Reza Ebrahimkhani, Narges Rashidi, Seyed Ali Gaskari, Ahmad Reza Dehpour

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalBrain Research
Volume1029
Issue number1
DOIs
StatePublished - Dec 10 2004

Keywords

  • Clonic seizure threshold
  • Lithium
  • Morphine
  • Mouse
  • Nitric oxide
  • Pentylenetetrazole

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Honar, H., Riazi, K., Homayoun, H., Demehri, S., Dehghani, M., Vafaie, K., Ebrahimkhani, M. R., Rashidi, N., Gaskari, S. A., & Dehpour, A. R. (2004). Lithium inhibits the modulatory effects of morphine on susceptibility to pentylenetetrazole-induced clonic seizure in mice: Involvement of a nitric oxide pathway. Brain Research, 1029(1), 48-55. https://doi.org/10.1016/j.brainres.2004.09.018