Ibrahim Ethem Torun, Yasemin Baranoglu Kilinc, Erkan Kilinc, Seyit Ankarali
{"title":"Spinorphin Attenuates Acute Experimental Seizures and Associated Neurochemical Alterations: Possible Involvement of Opioid Receptors","authors":"Ibrahim Ethem Torun, Yasemin Baranoglu Kilinc, Erkan Kilinc, Seyit Ankarali","doi":"10.1007/s11064-026-04923-3","DOIUrl":null,"url":null,"abstract":"<div><p>Spinorphin, an endogenous enkephalinase inhibitor, enhances physiological opioid signaling by preventing the degradation of endogenous enkephalins, however, its anticonvulsant potential has not previously been investigated. This study evaluated the effects of spinorphin on seizure activity and associated neurochemical alterations in two complementary acute experimental seizure models. The effects of spinorphin on seizure activity were investigated in pentylenetetrazole (PTZ)- and penicillin-induced acute seizure rat models. Behavioral seizure parameters, passive avoidance memory, electrocorticographic activity, cortical and hippocampal glutamate, GABA, c-Fos, calcitonin gene-related peptide (CGRP), inflammatory cytokines, and oxidative stress biomarkers were evaluated. Nalmefene was used to determine the contribution of opioid receptor signaling. Spinorphin significantly attenuated behavioral seizures, reduced cortical epileptiform spike frequency, and improved passive avoidance retention performance. It attenuated PTZ-induced alterations in cortical and hippocampal glutamate and GABA concentrations and reduced tissue levels of c-Fos and CGRP, together with changes in inflammatory and oxidative stress-related biomarkers in both the cortex and hippocampus. These effects were substantially attenuated by nalmefene, suggesting a possible contribution of endogenous opioid signaling, although the incomplete reversal indicates that additional opioid-independent mechanisms may also be involved. Spinorphin attenuates seizure activity and associated biochemical alterations in experimental seizure models. By enhancing the regional availability of endogenous enkephalins rather than directly activating opioid receptors, spinorphin may exert its anticonvulsant effects partly through endogenous opioid signaling, while additional opioid-independent mechanisms may also contribute. These findings provide a basis for further investigation of enkephalinase inhibition in experimental seizure models.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"51 6","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11064-026-04923-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Spinorphin, an endogenous enkephalinase inhibitor, enhances physiological opioid signaling by preventing the degradation of endogenous enkephalins, however, its anticonvulsant potential has not previously been investigated. This study evaluated the effects of spinorphin on seizure activity and associated neurochemical alterations in two complementary acute experimental seizure models. The effects of spinorphin on seizure activity were investigated in pentylenetetrazole (PTZ)- and penicillin-induced acute seizure rat models. Behavioral seizure parameters, passive avoidance memory, electrocorticographic activity, cortical and hippocampal glutamate, GABA, c-Fos, calcitonin gene-related peptide (CGRP), inflammatory cytokines, and oxidative stress biomarkers were evaluated. Nalmefene was used to determine the contribution of opioid receptor signaling. Spinorphin significantly attenuated behavioral seizures, reduced cortical epileptiform spike frequency, and improved passive avoidance retention performance. It attenuated PTZ-induced alterations in cortical and hippocampal glutamate and GABA concentrations and reduced tissue levels of c-Fos and CGRP, together with changes in inflammatory and oxidative stress-related biomarkers in both the cortex and hippocampus. These effects were substantially attenuated by nalmefene, suggesting a possible contribution of endogenous opioid signaling, although the incomplete reversal indicates that additional opioid-independent mechanisms may also be involved. Spinorphin attenuates seizure activity and associated biochemical alterations in experimental seizure models. By enhancing the regional availability of endogenous enkephalins rather than directly activating opioid receptors, spinorphin may exert its anticonvulsant effects partly through endogenous opioid signaling, while additional opioid-independent mechanisms may also contribute. These findings provide a basis for further investigation of enkephalinase inhibition in experimental seizure models.
期刊介绍：
Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
