The possible role of nitric oxide in anti-convulsant effects of Naltrindole in seizure-induced by social isolation stress in male mice

Biomed Pharmacother. 2020 Sep:129:110453. doi: 10.1016/j.biopha.2020.110453. Epub 2020 Jun 27.

Abstract

Social isolation stress (SIS) as a chronic model of early-life stress could induce proconvulsant effects in mice. In the current study, we evaluated the role of opioid receptors (OPRs) agonists and antagonists in pro-conversant effects of SIS and the common pathway between delta-opioid receptors (DORs) and nitric oxide (NO) in stress-induced seizure. For reaching to this goal, we used pentylenetetrazol (PTZ) model of clonic-seizure to measure seizure threshold and administrated selective and non-selective OPRs agonists and antagonists in both social condition (SC) and isolated condition (IC) animals. In the next step, we administrated sub effective dose of naltrindole (NLT, 0.3 mg/kg) with sub-effective doses of nitric oxide synthesis (NOS) inhibitors including L-NAME (10 mg/kg), aminoguanidine (50 mg/kg) and 7-NI (15 mg/kg). Also, we co-administrated sub-effective dose of SNC80 (0.5 mg/kg) with sub-effective dose of l-arg (25 mg/kg) to assess the seizure threshold. In addition, we measured nitrite levels of hippocampus following administration of mentioned drugs in both SC and IC mice. Our findings showed that L-NAME and 7-NI (but not AG) increased anti-convulsant activity of NLT and l-arg increased proconvulsant effects of SNC80 in IC animals. Nitrite assay showed that co-administration of NLT plus sub-effective doses of L-NAME and 7-NI (but not AG) decreased and co-administration of SNC80 with sub-effective dose of l-arg increased nitrite levels of hippocampus in IC mice. This study suggests the role of n-NOS in anti-convulsant effects of NLT and pro-convulsant effects of SNC80 in stress-induced seizure.

Keywords: Delta opioid receptor; Nitric oxide; Opioid system; Seizure; Social isolation stress.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Disease Models, Animal
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Male
  • Mice
  • Naltrexone / analogs & derivatives*
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type I / metabolism
  • Pentylenetetrazole
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, delta / metabolism
  • Seizures / etiology
  • Seizures / metabolism
  • Seizures / physiopathology
  • Seizures / prevention & control*
  • Signal Transduction
  • Social Isolation*
  • Stress, Psychological / complications*

Substances

  • Anticonvulsants
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Nitric Oxide
  • Naltrexone
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse
  • naltrindole
  • Pentylenetetrazole