{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:37Z","timestamp":1787028517862,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Foundation for Basic Research (RFBR)","award":["20-015-00327 A"],"award-info":[{"award-number":["20-015-00327 A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Depression is a severe and widespread psychiatric disease that often accompanies epilepsy. Antidepressant treatment of depression comorbid with epilepsy is a major concern due to the risk of seizure aggravation. SAMe, a universal methyl donor for DNA methylation and the synthesis of brain monoamines, is known to have high antidepressant activity. This study aimed to find out whether L-methionine (L-MET), a precursor of SAMe, can have antidepressant and\/or anxiolytic effects in the WAG\/Rij rat model of depression comorbid with absence epilepsy. The results indicate that L-MET reduces the level of anxiety and depression in WAG\/Rij rats and suppresses associated epileptic seizures, in contrast to conventional antidepressant imipramine, which aggravates absence seizures. The antidepressant effect of L-MET was comparable with that of the conventional antidepressants imipramine and fluoxetine. However, the antidepressant profile of L-MET was more similar to imipramine than to fluoxetine. Taken together, our findings suggest that L-MET could serve as a promising new antidepressant drug with anxiolytic properties for the treatment of depression comorbid with absence epilepsy. Increases in the level of monoamines and their metabolites\u2014DA, DOPAC, HVA, NA, and MHPG\u2014in several brain structures, is suggested to be a neurochemical mechanism of the beneficial phenotypic effect of L-MET.<\/jats:p>","DOI":"10.3390\/ijms241512425","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T09:27:48Z","timestamp":1691141268000},"page":"12425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antidepressant and Anxiolytic Effects of L-Methionine in the WAG\/Rij Rat Model of Depression Comorbid with Absence Epilepsy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-7003","authenticated-orcid":false,"given":"Karine Yu.","family":"Sarkisova","sequence":"first","affiliation":[{"name":"Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, Butlerova Str. 5A, Moscow 117485, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9359-1345","authenticated-orcid":false,"given":"Alexandra V.","family":"Gabova","sequence":"additional","affiliation":[{"name":"Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, Butlerova Str. 5A, Moscow 117485, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina A.","family":"Fedosova","sequence":"additional","affiliation":[{"name":"Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, Butlerova Str. 5A, Moscow 117485, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla B.","family":"Shatskova","sequence":"additional","affiliation":[{"name":"Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, Butlerova Str. 5A, Moscow 117485, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor B.","family":"Narkevich","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution \u201cScientific Research Institute of Pharmacology named after V.V. Zakusov\u201d, Baltiyskaya Str. 8, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir S.","family":"Kudrin","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Institution \u201cScientific Research Institute of Pharmacology named after V.V. Zakusov\u201d, Baltiyskaya Str. 8, Moscow 125315, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Saavedra, K., Molina-M\u00e1rquez, A., Saavedra, N., Zambrano, T., and Salazar, L. (2016). Epigenetic modifications of major depressive disorder. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081279"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1212\/CPJ.0000000000000874","article-title":"Psychiatric comorbidities in people with epilepsy","volume":"11","author":"Mula","year":"2020","journal-title":"Neurol. 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