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

• Main Authors: Rajan Nikbakhsh, Rambod Nikbakhsh, Mahla Radmard, Armin Tafazolimoghadam, Arvin Haj-Mirzaian, Fardad Pirri, Paniz Noormohammady, Maral Sabouri, Niloufar Shababi, Seyed Ali Ziai, Ahmad Reza Dehpour
• Format: Article
• Language: English
• Published: Elsevier 2020-09-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Social isolation stress; Seizure; Opioid system; Delta opioid receptor; Nitric oxide
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332220306466

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.