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Biomed Pharmacother ; 129: 110453, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32603891

RESUMO

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.


Assuntos
Anticonvulsivantes/farmacologia , Hipocampo/efeitos dos fármacos , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/farmacologia , Óxido Nítrico/metabolismo , Receptores Opioides delta/antagonistas & inibidores , Convulsões/prevenção & controle , Isolamento Social , Estresse Psicológico/complicações , Animais , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Camundongos , Naltrexona/farmacologia , Óxido Nítrico Sintase Tipo I/metabolismo , Pentilenotetrazol , Receptores Opioides delta/metabolismo , Convulsões/etiologia , Convulsões/metabolismo , Convulsões/fisiopatologia , Transdução de Sinais
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