Involvement of nitrergic system in anticonvulsant effect of zolpidem in lithium-pilocarpine induced status epilepticus: Evaluation of iNOS and COX-2 genes expression.

Abstract

This study aims to investigate the role of zolpidem in lithium-pilocarpine induced status epilepticus (SE) and probable mechanisms involved in seizure threshold alteration. In the present study, lithium chloride (127mg/kg) was administered 20h prior to pilocarpine (60mg/kg) to induce SE in adult male Wistar rats. Different doses of zolpidem (0.1, 1, 2, 5, 10mg/kg) were injected 30min before pilocarpine administration. Furthermore, to find out whether nitric oxide (NO) plays a role in the observed effect, L-arginine and L-NAME were injected 15min before zolpidem. Afterward, we identified the particular NO isoform mediating the effect of zolpidem by injecting aminoguanidine (AG) and 7-Nitroindazole (7-NI) 15min prior to zolpidem. Moreover, in both 6 and 24h after pilocarpine injection, experimental groups underwent hippocampectomy to evaluate cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes expression by quantitative reverse transcription-PCR (qRT-PCR). Pre-treatment with zolpidem significantly prevented the onset of SE in a dose-dependent manner. AG and L-NAME significantly potentiated the anticonvulsant effect of zolpidem while L-arginine inverted this effect. Our qRT-PCR exerted that there was a continuous elevation of iNOS and COX-2 genes expression over 6 and 24h after pilocarpine administration in SE and L-arginine+Zolpidem groups while in AG/L-NAME+Zolpidem and zolpidem groups this upregulation was prevented. Our study indicates that zolpidem prevents the onset of SE through inhibition of iNOS/COX-2 genes upregulation following lithium-pilocarpine administration. Consistent with our results, we suggest that iNOS activation could be probably upstream of COX-2 gene expression.

• Authors: Seyyed Majid Eslami, Maryam Ghasemi, Taraneh Bahremand, Majid Momeny, Mahdi Gholami, Mohammad Sharifzadeh, Ahmad Reza Dehpour
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 815 Pg. 454-461 (Nov 15 2017) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 28987270 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Pyridines
• Pilocarpine
• Zolpidem
• Arginine
• Lithium
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Anticonvulsants (pharmacology, therapeutic use)
• Arginine (pharmacology)
• Cyclooxygenase 2 (genetics)
• Dose-Response Relationship, Drug
• Drug Interactions
• Gene Expression Regulation, Enzymologic (drug effects)
• Lithium (pharmacology)
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase Type II (genetics)
• Pilocarpine (pharmacology)
• Pyridines (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Status Epilepticus (chemically induced, drug therapy, genetics, metabolism)
• Zolpidem